Congratulations! Mo Yan, Chinese First Nobel!

Following the announcement, Peter Englund, Permanent Secretary of the Swedish Academy, was interviewed by freelance journalist Sven Hugo Persson about the 2012 Nobel Prize in Literature to Mo Yan.

See a Video of the Interview
4 min.

Communication: Antibody-Linked Spherical Nucleic Acids for Cellular Targeting

Spherical nucleic acid (SNA) constructs are promising new single entity gene regulation materials capable of both cellular transfection and gene knockdown, but thus far are promiscuous structures, exhibiting excellent genetic but little cellular selectivity. In this communication, we describe a strategy to impart targeting capabilities to these constructs through noncovalent functionalization with a complementary antibody-DNA conjugate. As a proof-of-concept, we designed HER2-targeting SNAs and demonstrated that such structures exhibit cell type selectivity in terms of their uptake, and significantly greater gene knockdown in cells overexpressing the target antigen as compared to the analogous antibody-free and off-target materials.


Monoclonal Antibodies Used as Reagents in Drug Manufacturing

Monoclonal Antibodies Used as Reagents in Drug Manufacturing

This guidance is intended to provide recommendations to sponsors and applicants on the use of
monoclonal antibodies (mAbs) as reagents in the manufacture of drug substances2 that are regulated by
the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and
Research (CBER). The guidance focuses on the chemistry, manufacturing, and control (CMC) issues
that should be addressed in new drug applications (NDAs), abbreviated new drug applications
(ANDAs), biologics license applications (BLAs), supplements to these applications, or investigational
new drug applications (INDs).
This document presents issues associated with and recommendations on the documentation to support
the use of mAb reagents generated by hybridoma technology or production of recombinant mAb or
their fragments in bacteria, including phage display technology, fungi (yeasts and molds), and nonprimate
animal-derived transfected cell lines. Monoclonal antibodies or their fragments generated by other
methods can present additional concerns. The recommendations provided in this document should be
considered when such materials are used; however, the guidance does not address the particular
method of production of the mAbs or their fragments.
This document does not provide recommendations on mAbs that are used as diagnostics, radiolabeled
imaging agents, or therapeutic products. For a discussion of mAb products for human therapeutic or
diagnostic use please refer to the Points to Consider in the Manufacture and Testing of Monoclonal

Antibody Products for Human Use (PTC 1997).3 The recommendations for characterization and
testing for mAbs used as parenteral pharmaceuticals are by necessity stringent, and not all of them are
applicable to mAbs that are used as reagents in drug manufacturing.

More details, please click here: Monoclonal Antibodies Used as Reagents in Drug Manufacturing.

Glycosylation of recombinant antibody therapeutics.


The adaptive immune system has the capacity to produce antibodies with a virtually infinite repertoire of specificities. Recombinant antibodies specific for human targets are established in the clinic as therapeutics and represent a major new class of drug. Therapeutic efficacy depends on the formation of complexes with target molecules and subsequent activation of downstream biologic effector mechanisms that result in elimination of the target. The activation of effector mechanisms is dependent on structural characteristics of the antibody molecule that result from posttranslational modifications, in particular, glycosylation. The production of therapeutic antibody with a consistent human glycoform profile has been and remains a considerable challenge to the biopharmaceutical industry. Recent research has shown that individual glycoforms of antibody may provide optimal efficacy for selected outcomes. Thus a further challenge will be the production of a second generation of antibody therapeutics customized for their clinical indication.

PMID: 15903235 [PubMed – indexed for MEDLINE]

What Is a Recombinant Antibody?

A recombinant antibody is an antibody made through the use of recombinant DNA technology by inserting a fragment of DNA into a yeast, virus, or bacterium. The resulting recombinant organism will express the antibody even if it is from a different species. A researcher can harvest the antibodies for medical experimentation and research. It is also possible to use them in the preparation of pharmaceutical compounds to treat various diseases.

Recombinant DNA technology requires a lab environment where researchers can work with a variety of organisms and vectors. The vector acts as a carrier for the DNA of interest. The researcher can select the most appropriate organism and vector on the basis of the genetic material and past successes or failures. She carefully inserts the DNA into that of the organism to force it to clone and express the antibody. With controlled conditions, she can breed multiple generations of organisms that will all produce the recombinant antibody.

Some scientific companies make and sell recombinant antibodies. Researchers who want to work with them but do not have the technology to create them can place an order for a standard or custom product. The company will produce the organisms and send a finished product to the scientist. It can also work with a researcher who wants to develop a new recombinant antibody or who needs a customized product for a very specific need.

These antibodies can be valuable for pure research as well as pharmaceutical research and development. It can be possible to use recombinant antibodies in antigen screenings, to identify reactive antigens in a sample. They can also be useful for the treatment of disease. A patient can take a recombinant antibody to fight off an organism her body cannot identify and isolate on its own. This is one approach to cancer treatment, where patients take medications that target cancerous cells and leave the rest alone.

Very controlled conditions are necessary for recombinant antibody production. The researcher needs to make sure that the DNA fragment is complete and comes from the correct section of the genome. If it is wrong or there is an error in the DNA, the resulting antibodies may not be usable or could behave unexpectedly. Introduction of contaminants can also cause problems with antibody production, as organisms may produce the wrong substance or could fail to thrive because of an accidental DNA insertion. Researchers routinely test the output from their labs to confirm that it is pure and usable.

Recombinant antibodies: engineering and production in yeast and bacterial hosts.


After the appearance of the first FDA-approved antibody 25 years ago, antibodies have become major therapeutic agents in the treatment of many human diseases, including cancer and infectious diseases, and the use of antibodies as therapeutic/diagnostic agents is expected to increase in the future. So far, a variety of strategies have been devised for engineering of these fascinating molecules to develop superior properties and functions. Recent progress in systems biology has provided more information about the structures and cellular networks of antibodies, and, in addition, recent development of biotechnology tools, particularly in regard to high-throughput screening, has made it possible to perform more intensive engineering on these substances. Based on a sound understanding and new technologies, antibodies are now being developed as more powerful drugs. In this review, we highlight the recent, significant progress that has been made in antibody engineering, with a particular focus on Fc engineering and glycoengineering for improved functions, and cellular engineering for enhanced production of antibodies in yeast and bacterial hosts.


From Wikipedia, the free encyclopedia
“Immunoglobulin” redirects here. For the immunoglobulin family, see Immunoglobulin superfamily.
“Antibodies” redirects here. For the film, see Antibodies (film). For the TV-movie, see Antibody (film).

Each antibody binds to a specific antigen; an interaction similar to a lock and key.

An antibody (Ab), also known as an immunoglobulin (Ig), is a large Y-shaped protein produced by B-cells that is used by the immune systemto identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, called anantigen.[1][2] Each tip of the “Y” of an antibody contains a paratope (a structure analogous to a lock) that is specific for one particular epitope(similarly analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly (for example, by blocking a part of a microbe that is essential for its invasion and survival). The production of antibodies is the main function of the humoral immune system.[3]

Antibodies are produced by a type of white blood cell called a plasma cell. Antibodies can occur in two physical forms, a soluble form that is secreted from the cell, and a membrane-bound form that is attached to the surface of a B cell and is referred to as the B cell receptor (BCR). The BCR is only found on the surface of B cells and facilitates the activation of these cells and their subsequent differentiation into either antibody factories called plasma cells, or memory B cells that will survive in the body and remember that same antigen so the B cells can respond faster upon future exposure.[4] In most cases, interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell and, therefore, antibody generation following antigen binding.[5] Soluble antibodies are released into the blood and tissue fluids, as well as manysecretions to continue to survey for invading microorganisms.

Antibodies are glycoproteins belonging to the immunoglobulin superfamily; the terms antibody and immunoglobulin are often used interchangeably.[6] Antibodies are typically made of basic structural units—each with two large heavy chains and two small light chains. There are several different types of antibody heavy chains, and several different kinds of antibodies, which are grouped into different isotypes based on which heavy chain they possess. Five different antibody isotypes are known in mammals, which perform different roles, and help direct the appropriate immune response for each different type of foreign object they encounter.[7]

Though the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures, or antigen binding sites, to exist. This region is known as the hypervariable region. Each of these variants can bind to a different target, known as an antigen.[1] This enormous diversity of antibodies allows the immune system to recognize an equally wide variety of antigens.[6] The large and diverse population of antibodies is generated by random combinations of a set of gene segments that encode different antigen binding sites (orparatopes), followed by random mutations in this area of the antibody gene, which create further diversity.[7][8] Antibody genes also re-organize in a process called class switching that changes the base of the heavy chain to another, creating a different isotype of the antibody that retains the antigen specific variable region. This allows a single antibody to be used by several different parts of the immune system.


Surface immunoglobulin (Ig) is attached to the membrane of the effector B cells by its transmembrane region, while antibodies are the secreted form of Ig and lack the trans membrane region so that antibodies can be secreted into the bloodstream and body cavities. As a result, surface Ig and antibodies are identical except for the transmembrane regions. Therefore, they are considered two forms of antibodies: soluble form or membrane-bound form (Parham 21-22).

The membrane-bound form of an antibody may be called a surface immunoglobulin (sIg) or a membrane immunoglobulin (mIg). It is part of the B cell receptor (BCR), which allows a B cell to detect when a specific antigen is present in the body and triggers B cell activation.[9] The BCR is composed of surface-bound IgD or IgM antibodies and associated Ig-α and Ig-β heterodimers, which are capable of signal transduction.[10] A typical human B cell will have 50,000 to 100,000 antibodies bound to its surface.[10] Upon antigen binding, they cluster in large patches, which can exceed 1 micrometer in diameter, on lipid rafts that isolate the BCRs from most other cell signaling receptors.[10] These patches may improve the efficiency of the cellular immune response.[11] In humans, the cell surface is bare around the B cell receptors for several hundred nanometers,[12] which further isolates the BCRs from competing influences.


Antibody isotypes of mammals
Name Types Description Antibody Complexes
IgA 2 Found in mucosal areas, such as the gutrespiratory tract and urogenital tract, and prevents colonization by pathogens.[13] Also found in saliva, tears, and breast milk. Some antibodies form complexes that bind to multiple antigen molecules.
IgD 1 Functions mainly as an antigen receptor on B cells that have not been exposed to antigens.[14] It has been shown to activate basophils and mast cells to produce antimicrobial factors.[15]
IgE 1 Binds to allergens and triggers histamine release from mast cells and basophils, and is involved in allergy. Also protects against parasitic worms.[3]
IgG 4 In its four forms, provides the majority of antibody-based immunity against invading pathogens.[3] The only antibody capable of crossing the placenta to give passive immunity to fetus.
IgM 1 Expressed on the surface of B cells (monomer) and in a secreted form (pentamer) with very high avidity. Eliminates pathogens in the early stages of B cell mediated (humoral) immunity before there is sufficient IgG.[3][14]

Antibodies can come in different varieties known as isotypes or classes. In placental mammals there are five antibody isotypes known as IgA, IgD, IgE, IgG and IgM. They are each named with an “Ig” prefix that stands for immunoglobulin, another name for antibody, and differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in the table.[16]

The antibody isotype of a B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, are known as naïve B cells and express only the IgM isotype in a cell surface bound form. B cells begin to express both IgM and IgD when they reach maturity—the co-expression of both these immunoglobulin isotypes renders the B cell ‘mature’ and ready to respond to antigen.[17] B cell activation follows engagement of the cell bound antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody producing cell called a plasma cell. In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane-bound form. Some daughter cells of the activated B cells undergo isotype switching, a mechanism that causes the production of antibodies to change from IgM or IgD to the other antibody isotypes, IgE, IgA or IgG, that have defined roles in the immune system.


Antibodies are heavy (~150 kDaglobular plasma proteins. They have sugar chains added to some of their amino acid residues.[18] In other words, antibodies are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM.[19]

Several immunoglobulin domains make up the two heavy chains (red and blue) and the two light chains (green and yellow) of an antibody. The immunoglobulin domains are composed of between 7 (for constant domains) and 9 (for variable domains) β-strands.

The variable parts of an antibody are its V regions, and the constant part is its C region.


Immunoglobulin domains

The Ig monomer is a “Y”-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds.[16] Each chain is composed of structural domains called immunoglobulin domains. These domains contain about 70-110 amino acids and are classified into different categories (for example, variable or IgV, and constant or IgC) according to their size and function.[20] They have a characteristic immunoglobulin fold in which two beta sheets create a “sandwich” shape, held together by interactions between conserved cysteines and other charged amino acids.

Heavy chain

For more details on this topic, see Immunoglobulin heavy chain.

There are five types of mammalian Ig heavy chain denoted by the Greek letters: α, δ, ε, γ, and μ.[1] The type of heavy chain present defines the class of antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.[6] Distinct heavy chains differ in size and composition; α and γ contain approximately 450 amino acids, while μ and ε have approximately 550 amino acids.[1]

1. Fab region
2. Fc region
3. Heavy chain (blue) with one variable (VH) domain followed by a constant domain (CH1), a hinge region, and two more constant (CH2 and CH3) domains.
4. Light chain (green) with one variable (VL) and one constant (CL) domain
5. Antigen binding site (paratope)
6. Hinge regions.

In birds, the major serum antibody, also found in yolk, is called IgY. It is quite different from mammalian IgG. However, in some older literature and even on some commercial life sciences product websites it is still called “IgG”, which is incorrect and can be confusing.

Each heavy chain has two regions, the constant region and the variable region. The constant region is identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, α and δ have a constant region composed of three tandem (in a line) Ig domains, and a hinge region for added flexibility;[16] heavy chains μ and ε have a constant region composed of four immunoglobulin domains.[1] The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain.

Light chain

For more details on this topic, see Immunoglobulin light chain.

In mammals there are two types of immunoglobulin light chain, which are called lambda (λ) and kappa (κ).[1] A light chain has two successive domains: one constant domain and one variable domain. The approximate length of a light chain is 211 to 217 amino acids.[1] Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody in mammals. Other types of light chains, such as the iota (ι) chain, are found in lower vertebrates like sharks (Chondrichthyes) and bony fishes (Teleostei).

CDRs, Fv, Fab and Fc Regions

Some parts of an antibody have unique functions. The arms of the Y, for example, contain the sites that can bind two antigens (in general, identical) and, therefore, recognize specific foreign objects. This region of the antibody is called the Fab (fragment, antigen binding) region. It is composed of one constant and one variable domain from each heavy and light chain of the antibody.[21] The paratope is shaped at the amino terminal end of the antibodymonomer by the variable domains from the heavy and light chains. The variable domain is also referred to as the FV region and is the most important region for binding to antigens. More specifically, variable loops of β-strands, three each on the light (VL) and heavy (VH) chains are responsible for binding to the antigen. These loops are referred to as the complementarity determining regions (CDRs). The structures of these CDRs have been clustered and classified by Chothia et al.[22] and more recently by North et al.[23] In the framework of the immune network theory, CDRs are also called idiotypes. According to immune network theory, the adaptive immune system is regulated by interactions between idiotypes.

The base of the Y plays a role in modulating immune cell activity. This region is called the Fc (Fragment, crystallizable) region, and is composed of two heavy chains that contribute two or three constant domains depending on the class of the antibody.[1] Thus, the Fc region ensures that each antibody generates an appropriate immune response for a given antigen, by binding to a specific class of Fc receptors, and other immune molecules, such as complement proteins. By doing this, it mediates different physiological effects including recognition of opsonized particles,lysis of cells, and degranulation of mast cellsbasophils and eosinophils.[16][24]


Further information: Immune system

Activated B cells differentiate into either antibody-producing cells called plasma cells that secrete soluble antibody or memory cells that survive in the body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures.[25]

At the prenatal and neonatal stages of life, the presence of antibodies is provided by passive immunization from the mother. Early endogenous antibody production varies for different kinds of antibodies, and usually appear within the first years of life. Since antibodies exist freely in the bloodstream, they are said to be part of the humoral immune system. Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus capsid protein fragment). Antibodies contribute to immunity in three ways: they prevent pathogens from entering or damaging cells by binding to them; they stimulate removal of pathogens by macrophages and other cells by coating the pathogen; and they trigger destruction of pathogens by stimulating other immune responses such as the complement pathway.[26]

The secreted mammalian IgM has five Ig units. Each Ig unit (labeled 1) has two epitope binding Fab regions, so IgM is capable of binding up to 10 epitopes.

Activation of complement

Antibodies that bind to surface antigens on, for example, a bacterium attract the first component of the complement cascade with their Fc region and initiate activation of the “classical” complement system.[26] This results in the killing of bacteria in two ways.[3] First, the binding of the antibody and complement molecules marks the microbe for ingestion by phagocytes in a process called opsonization; these phagocytes are attracted by certain complement molecules generated in the complement cascade. Secondly, some complement system components form a membrane attack complex to assist antibodies to kill the bacterium directly.[27]

Activation of effector cells

To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them together, causing them to agglutinate. Since an antibody has at least two paratopes it can bind more than one antigen by binding identical epitopes carried on the surfaces of these antigens. By coating the pathogen, antibodies stimulate effector functions against the pathogen in cells that recognize their Fc region.[3]

Those cells which recognize coated pathogens have Fc receptors which, as the name suggests, interacts with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell; phagocytes willphagocytosemast cells and neutrophils will degranulatenatural killer cells will release cytokines and cytotoxic molecules; that will ultimately result in destruction of the invading microbe. The Fc receptors are isotype-specific, which gives greater flexibility to the immune system, invoking only the appropriate immune mechanisms for distinct pathogens.[1]

Natural antibodies

Humans and higher primates also produce “natural antibodies” which are present in serum before viral infection. Natural antibodies have been defined as antibodies that are produced without any previous infection, vaccination, other foreign antigen exposure or passive immunization. These antibodies can activate the classical complement pathway leading to lysis of enveloped virus particles long before the adaptive immune response is activated. Many natural antibodies are directed against the disaccharide galactose α(1,3)-galactose (α-Gal), which is found as a terminal sugar on glycosylated cell surface proteins, and generated in response to production of this sugar by bacteria contained in the human gut.[28] Rejection of xenotransplantated organs is thought to be, in part, the result of natural antibodies circulating in the serum of the recipient binding to α-Gal antigens expressed on the donor tissue.[29]

Immunoglobulin diversity

Virtually all microbes can trigger an antibody response. Successful recognition and eradication of many different types of microbes requires diversity among antibodies; their amino acid composition varies allowing them to interact with many different antigens.[30] It has been estimated that humans generate about 10 billion different antibodies, each capable of binding a distinct epitope of an antigen.[31] Although a huge repertoire of different antibodies is generated in a single individual, the number of genes available to make these proteins is limited by the size of the human genome. Several complex genetic mechanisms have evolved that allow vertebrate B cells to generate a diverse pool of antibodies from a relatively small number of antibody genes.[32]

Domain variability

The complementarity determining regions of the heavy chain are shown in red (PDB 1IGT)

The region (locus) of a chromosome that encodes an antibody is large and contains several distinct genes for each domain of the antibody—the locus containing heavy chain genes (IGH@) is found on chromosome 14, and the loci containing lambda and kappa light chain genes (IGL@ andIGK@) are found on chromosomes 22 and 2 in humans. One of these domains is called the variable domain, which is present in each heavy and light chain of every antibody, but can differ in different antibodies generated from distinct B cells. Differences, between the variable domains, are located on three loops known as hypervariable regions (HV-1, HV-2 and HV-3) or complementarity determining regions (CDR1, CDR2 and CDR3). CDRs are supported within the variable domains by conserved framework regions. The heavy chain locus contains about 65 different variable domain genes that all differ in their CDRs. Combining these genes with an array of genes for other domains of the antibody generates a large cavalry of antibodies with a high degree of variability. This combination is called V(D)J recombination discussed below.[33]

V(D)J recombination

For more details on this topic, see V(D)J recombination.

Simplified overview of V(D)J recombination of immunoglobulin heavy chains

Somatic recombination of immunoglobulins, also known as V(D)J recombination, involves the generation of a unique immunoglobulin variable region. The variable region of each immunoglobulin heavy or light chain is encoded in several pieces—known as gene segments (subgenes). These segments are called variable (V), diversity (D) and joining (J) segments.[32] V, D and J segments are found in Ig heavy chains, but only V and J segments are found in Ig light chains. Multiple copies of the V, D and J gene segments exist, and are tandemly arranged in the genomes ofmammals. In the bone marrow, each developing B cell will assemble an immunoglobulin variable region by randomly selecting and combining one V, one D and one J gene segment (or one V and one J segment in the light chain). As there are multiple copies of each type of gene segment, and different combinations of gene segments can be used to generate each immunoglobulin variable region, this process generates a huge number of antibodies, each with different paratopes, and thus different antigen specificities.[7] Interestingly, the rearrangement of several subgenes (e.i. V2 family) for lambda light chain immunoglobulin is coupled with the activation of microRNA miR-650, which further influences biology of B-cells .[34]

After a B cell produces a functional immunoglobulin gene during V(D)J recombination, it cannot express any other variable region (a process known as allelic exclusion) thus each B cell can produce antibodies containing only one kind of variable chain.[1][35]

Somatic hypermutation and affinity maturation

For more details on this topic, see Somatic hypermutation and Affinity maturation

Following activation with antigen, B cells begin to proliferate rapidly. In these rapidly dividing cells, the genes encoding the variable domains of the heavy and light chains undergo a high rate of point mutation, by a process called somatic hypermutation (SHM). SHM results in approximately onenucleotide change per variable gene, per cell division.[8] As a consequence, any daughter B cells will acquire slight amino acid differences in the variable domains of their antibody chains.

This serves to increase the diversity of the antibody pool and impacts the antibody’s antigen-binding affinity.[36] Some point mutations will result in the production of antibodies that have a weaker interaction (low affinity) with their antigen than the original antibody, and some mutations will generate antibodies with a stronger interaction (high affinity).[37] B cells that express high affinity antibodies on their surface will receive a strong survival signal during interactions with other cells, whereas those with low affinity antibodies will not, and will die by apoptosis.[37] Thus, B cells expressing antibodies with a higher affinity for the antigen will outcompete those with weaker affinities for function and survival. The process of generating antibodies with increased binding affinities is called affinity maturation. Affinity maturation occurs in mature B cells after V(D)J recombination, and is dependent on help from helper T cells.[38]

Class switching

Isotype or class switching is a biological process occurring after activation of the B cell, which allows the cell to produce different classes of antibody (IgA, IgE, or IgG).[7] The different classes of antibody, and thus effector functions, are defined by the constant (C) regions of the immunoglobulin heavy chain. Initially, naïve B cells express only cell-surface IgM and IgD with identical antigen binding regions. Each isotype is adapted for a distinct function, therefore, after activation, an antibody with an IgG, IgA, or IgE effector function might be required to effectively eliminate an antigen. Class switching allows different daughter cells from the same activated B cell to produce antibodies of different isotypes. Only the constant region of the antibody heavy chain changes during class switching; the variable regions, and therefore antigen specificity, remain unchanged. Thus the progeny of a single B cell can produce antibodies, all specific for the same antigen, but with the ability to produce the effector function appropriate for each antigenic challenge. Class switching is triggered by cytokines; the isotype generated depends on which cytokines are present in the B cell environment.[39]

Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR). This mechanism relies on conserved nucleotide motifs, called switch (S) regions, found in DNA upstream of each constant region gene (except in the δ-chain). The DNA strand is broken by the activity of a series of enzymes at two selected S-regions.[40][41] The variable domain exon is rejoined through a process called non-homologous end joining (NHEJ) to the desired constant region (γ, α or ε). This process results in an immunoglobulin gene that encodes an antibody of a different isotype.[42]

Affinity designations

A group of antibodies can be called monovalent (or specific) if they have affinity for the same epitope,[43] or for the same antigen[44] (but potentially different epitopes on the molecule), or for the same strain of microorganism[44] (but potentially different antigens on or in it). In contrast, a group of antibodies can be called polyvalent (or unspecific) if they have affinity for various antigens[45] or microorganisms.[45] Intravenous immunoglobulin, if not otherwise noted, consists of polyvalent IgG. In contrast, monoclonal antibodies are monovalent for the same epitope.

Medical applications

Disease diagnosis and therapy

Detection of particular antibodies is a very common form of medical diagnostics, and applications such as serology depend on these methods.[46] For example, in biochemical assays for disease diagnosis,[47] a titer of antibodies directed against Epstein-Barr virus or Lyme disease is estimated from the blood. If those antibodies are not present, either the person is not infected, or the infection occurred a very long time ago, and the B cells generating these specific antibodies have naturally decayed. In clinical immunology, levels of individual classes of immunoglobulins are measured by nephelometry (or turbidimetry) to characterize the antibody profile of patient.[48] Elevations in different classes of immunoglobulins are sometimes useful in determining the cause ofliver damage in patients for whom the diagnosis is unclear.[6] For example, elevated IgA indicates alcoholic cirrhosis, elevated IgM indicates viral hepatitis and primary biliary cirrhosis, while IgG is elevated in viral hepatitis, autoimmune hepatitis and cirrhosis. Autoimmune disorders can often be traced to antibodies that bind the body’s own epitopes; many can be detected through blood tests. Antibodies directed against red blood cell surface antigens in immune mediated hemolytic anemia are detected with the Coombs test.[49] The Coombs test is also used for antibody screening in blood transfusion preparation and also for antibody screening in antenatal women.[49] Practically, several immunodiagnostic methods based on detection of complex antigen-antibody are used to diagnose infectious diseases, for example ELISAimmunofluorescenceWestern blotimmunodiffusionimmunoelectrophoresis, and magnetic immunoassay. Antibodies raised against human chorionic gonadotropin are used in over the counter pregnancy tests. Targeted monoclonal antibody therapy is employed to treat diseases such as rheumatoid arthritis,[50] multiple sclerosis,[51] psoriasis,[52] and many forms of cancer including non-Hodgkin’s lymphoma,[53] colorectal cancerhead and neck cancer and breast cancer.[54] Some immune deficiencies, such asX-linked agammaglobulinemia and hypogammaglobulinemia, result in partial or complete lack of antibodies.[55] These diseases are often treated by inducing a short term form of immunity calledpassive immunity. Passive immunity is achieved through the transfer of ready-made antibodies in the form of human or animal serum, pooled immunoglobulin or monoclonal antibodies, into the affected individual.[56]

Prenatal therapy

Rhesus factor, also known as Rhesus D (RhD) antigen, is an antigen found on red blood cells; individuals that are Rhesus-positive (Rh+) have this antigen on their red blood cells and individuals that are Rhesus-negative (Rh–) do not. During normal childbirth, delivery trauma or complications during pregnancy, blood from a fetus can enter the mother’s system. In the case of an Rh-incompatible mother and child, consequential blood mixing may sensitize an Rh- mother to the Rh antigen on the blood cells of the Rh+ child, putting the remainder of the pregnancy, and any subsequent pregnancies, at risk for hemolytic disease of the newborn.[57]

Rho(D) immune globulin antibodies are specific for human Rhesus D (RhD) antigen.[58] Anti-RhD antibodies are administered as part of a prenatal treatment regimen to prevent sensitization that may occur when a Rhesus-negative mother has a Rhesus-positive fetus. Treatment of a mother with Anti-RhD antibodies prior to and immediately after trauma and delivery destroys Rh antigen in the mother’s system from the fetus. Importantly, this occurs before the antigen can stimulate maternal B cells to “remember” Rh antigen by generating memory B cells. Therefore, her humoral immune system will not make anti-Rh antibodies, and will not attack the Rhesus antigens of the current or subsequent babies. Rho(D) Immune Globulin treatment prevents sensitization that can lead to Rh disease, but does not prevent or treat the underlying disease itself.[58]

Research applications

Immunofluorescence image of the eukaryotic cytoskeletonActin filaments are shown in red, microtubules in green, and the nuclei in blue.

Specific antibodies are produced by injecting an antigen into a mammal, such as a mouseratrabbitgoatsheep, or horse for large quantities of antibody. Blood isolated from these animals contains polyclonal antibodies—multiple antibodies that bind to the same antigen—in the serum, which can now be called antiserum. Antigens are also injected into chickens for generation of polyclonal antibodies in egg yolk.[59] To obtain antibody that is specific for a single epitope of an antigen, antibody-secreting lymphocytes are isolated from the animal and immortalized by fusing them with a cancer cell line. The fused cells are called hybridomas, and will continually grow and secrete antibody in culture. Single hybridoma cells are isolated by dilution cloning to generate cell clones that all produce the same antibody; these antibodies are called monoclonal antibodies.[60] Polyclonal and monoclonal antibodies are often purified using Protein A/G or antigen-affinity chromatography.[61]

In research, purified antibodies are used in many applications. They are most commonly used to identify and locate intracellular and extracellular proteins. Antibodies are used in flow cytometry to differentiate cell types by the proteins they express; different types of cell express different combinations of cluster of differentiation molecules on their surface, and produce different intracellular and secretable proteins.[62] They are also used in immunoprecipitation to separate proteins and anything bound to them (co-immunoprecipitation) from other molecules in a cell lysate,[63] in Western blot analyses to identify proteins separated by electrophoresis,[64] and in immunohistochemistry or immunofluorescence to examine protein expression in tissue sections or to locate proteins within cells with the assistance of a microscope.[62][65] Proteins can also be detected and quantified with antibodies, using ELISA andELISPOT techniques.[66][67]

Structure prediction

The importance of antibodies in health care and the biotechnology industry demands knowledge of their structures at high resolution. This information is used for protein engineering, modifying the antigen binding affinity, and identifying an epitope, of a given antibody. X-ray crystallography is one commonly used method for determining antibody structures. However, crystallizing an antibody is often laborious and time consuming. Computational approaches provide a cheaper and faster alternative to crystallography, but their results are more equivocal since they do not produce empirical structures. Online web servers such as Web Antibody Modeling (WAM)[68] and Prediction of Immunoglobulin Structure (PIGS)[69] enables computational modeling of antibody variable regions. Rosetta Antibody is a novel antibody FV region structure prediction server, which incorporates sophisticated techniques to minimize CDR loops and optimize the relative orientation of the light and heavy chains, as well as homology models that predict successful docking of antibodies with their unique antigen.[70]


The first use of the term “antibody” occurred in a text by Paul Ehrlich. The term Antikörper (the German word for antibody) appears in the conclusion of his article “Experimental Studies on Immunity”, published in October 1891, which states that “if two substances give rise to two different antikörper, then they themselves must be different”.[71] However, the term was not accepted immediately and several other terms for antibody were proposed; these included ImmunkörperAmboceptorZwischenkörpersubstance sensibilisatricecopulaDesmonphilocytasefixateur, and Immunisin.[71] The word antibody has formal analogy to the word antitoxin and a similar concept to Immunkörper.[71]

Angel of the West (2008) by Julian Voss-Andreae is a sculpture based on the antibody structure published by E. Padlan.[72] Created for the Florida campus of the Scripps Research Institute,[73] the antibody is placed into a ring referencing Leonardo da Vinci’s Vitruvian Manthus highlighting the similar proportions of the antibody and the human body.[74]

The study of antibodies began in 1890 when Kitasato Shibasaburō described antibody activity against diphtheria and tetanus toxins. Kitasato put forward the theory of humoral immunity, proposing that a mediator in serum could react with a foreign antigen.[75][76] His idea prompted Paul Ehrlich to propose the side chain theory for antibody and antigen interaction in 1897, when he hypothesized that receptors (described as “side chains”) on the surface of cells could bind specifically to toxins – in a “lock-and-key” interaction – and that this binding reaction was the trigger for the production of antibodies.[77] Other researchers believed that antibodies existed freely in the blood and, in 1904, Almroth Wright suggested that soluble antibodies coated bacteria to label them for phagocytosis and killing; a process that he named opsoninization.[78]

Michael Heidelberger

In the 1920s, Michael Heidelberger and Oswald Avery observed that antigens could be precipitated by antibodies and went on to show that antibodies were made of protein.[79] The biochemical properties of antigen-antibody binding interactions were examined in more detail in the late 1930s by John Marrack.[80]The next major advance was in the 1940s, when Linus Pauling confirmed the lock-and-key theory proposed by Ehrlich by showing that the interactions between antibodies and antigens depended more on their shape than their chemical composition.[81] In 1948, Astrid Fagreaus discovered that B cells, in the form of plasma cells, were responsible for generating antibodies.[82]

Further work concentrated on characterizing the structures of the antibody proteins. A major advance in these structural studies was the discovery in the early 1960s by Gerald Edelman and Joseph Gally of the antibody light chain,[83] and their realization that this protein was the same as the Bence-Jones proteindescribed in 1845 by Henry Bence Jones.[84] Edelman went on to discover that antibodies are composed ofdisulfide bond-linked heavy and light chains. Around the same time, antibody-binding (Fab) and antibody tail (Fc) regions of IgG were characterized byRodney Porter.[85] Together, these scientists deduced the structure and complete amino acid sequence of IgG, a feat for which they were jointly awarded the 1972 Nobel Prize in Physiology or Medicine.[85] The Fv fragment was prepared and characterized by David Givol.[86] While most of these early studies focused on IgM and IgG, other immunoglobulin isotypes were identified in the 1960s: Thomas Tomasi discovered secretory antibody (IgA)[87] and David S. Rowe and John L. Fahey identified IgD,[88] and IgE was identified by Kimishige Ishizaka and Teruko Ishizaka as a class of antibodies involved in allergic reactions.[89] In a landmark series of experiments beginning in 1976, Susumu Tonegawa showed that genetic material can rearrange itself to form the vast array of available antibodies.[90]

See also


  1. a b c d e f g h i j Charles Janeway (2001). Immunobiology. (5th ed.). Garland Publishing.ISBN 0-8153-3642-X(electronic full text via NCBI Bookshelf).
  2. ^ Litman GW, Rast JP, Shamblott MJ, Haire RN, Hulst M, Roess W, Litman RT, Hinds-Frey KR, Zilch A, Amemiya CT (January 1993). “Phylogenetic diversification of immunoglobulin genes and the antibody repertoire”. Mol. Biol. Evol. 10 (1): 60–72. PMID 8450761.
  3. a b c d e f Pier GB, Lyczak JB, Wetzler LM (2004). Immunology, Infection, and Immunity. ASM Press. ISBN 1-55581-246-5.
  4. ^ Borghesi L, Milcarek C (2006). “From B cell to plasma cell: regulation of V(D)J recombination and antibody secretion”. Immunol. Res. 36 (1–3): 27–32. doi:10.1385/IR:36:1:27.PMID 17337763.
  5. ^ Parker D (1993). “T cell-dependent B cell activation”. Annu Rev Immunol 11 (1): 331–360.doi:10.1146/annurev.iy.11.040193.001555PMID 8476565.
  6. a b c d Rhoades RA, Pflanzer RG (2002). Human Physiology (4th ed.). Thomson Learning.ISBN 0-534-42174-1.
  7. a b c d Market E, Papavasiliou FN (October 2003). “V(D)J recombination and the evolution of the adaptive immune system”PLoS Biol. 1 (1): E16. doi:10.1371/journal.pbio.0000016.PMC 212695PMID 14551913.
  8. a b Diaz M, Casali P (2002). “Somatic immunoglobulin hypermutation”. Curr Opin Immunol 14(2): 235–240. doi:10.1016/S0952-7915(02)00327-8PMID 11869898.
  9. ^ Parker D (1993). “T cell-dependent B cell activation”. Annu. Rev. Immunol. 11 (1): 331–360.doi:10.1146/annurev.iy.11.040193.001555PMID 8476565.
  10. a b c Wintrobe, Maxwell Myer (2004). Wintrobe’s clinical hematology. John G. Greer, John Foerster, John N Lukens, George M Rodgers, Frixos Paraskevas (11 ed.). Hagerstown, MD: Lippincott Williams & Wilkins. pp. 453–456. ISBN 978-0-7817-3650-3.
  11. ^ Tolar P, Sohn HW, Pierce SK (February 2008). “Viewing the antigen-induced initiation of B-cell activation in living cells”Immunol. Rev. 221 (1): 64–76. doi:10.1111/j.1600-065X.2008.00583.xPMID 18275475.
  12. ^ Wintrobe, Maxwell Myer (2004). Wintrobe’s clinical hematology. John G. Greer, John Foerster, John N Lukens, George M Rodgers, Frixos Paraskevas (11 ed.). Hagerstown, MD: Lippincott Williams & Wilkins. pp. 453–456. ISBN 0-7817-3650-1.
  13. ^ Underdown B, Schiff J (1986). “Immunoglobulin A: strategic defense initiative at the mucosal surface”. Annu Rev Immunol 4 (1): 389–417. doi:10.1146/annurev.iy.04.040186.002133.PMID 3518747.
  14. a b Geisberger R, Lamers M, Achatz G (2006). “The riddle of the dual expression of IgM and IgD”Immunology 118 (4): 060526021554006––. doi:10.1111/j.1365-2567.2006.02386.x.PMC 1782314PMID 16895553.
  15. ^ Chen K, Xu W, Wilson M, He B, Miller NW, Bengtén E, Edholm ES, Santini PA, Rath P, Chiu A, Cattalini M, Litzman J, B Bussel J, Huang B, Meini A, Riesbeck K, Cunningham-Rundles C, Plebani A, Cerutti A (2009). “Immunoglobulin D enhances immune surveillance by activatingantimicrobialproinflammatory and B cell-stimulating programs in basophils”. Nature Immunology 10 (8): 889–898. doi:10.1038/ni.1748PMC 2785232PMID 19561614.
  16. a b c d Woof J, Burton D (2004). “Human antibody-Fc receptor interactions illuminated by crystal structures.”. Nat Rev Immunol 4 (2): 89–99. doi:10.1038/nri1266PMID 15040582.
  17. ^ Goding J (1978). “Allotypes of IgM and IgD receptors in the mouse: a probe for lymphocyte differentiation”. Contemp Top Immunobiol 8: 203–43. PMID 357078.
  18. ^ Mattu T, Pleass R, Willis A, Kilian M, Wormald M, Lellouch A, Rudd P, Woof J, Dwek R (1998). “The glycosylation and structure of human serum IgA1, Fab, and Fc regions and the role of N-glycosylation on Fc alpha receptor interactions”. J Biol Chem 273 (4): 2260–2272.doi:10.1074/jbc.273.4.2260PMID 9442070.
  19. ^ Roux K (1999). “Immunoglobulin structure and function as revealed by electron microscopy”.Int Arch Allergy Immunol 120 (2): 85–99. doi:10.1159/000024226PMID 10545762.
  20. ^ Barclay A (2003). “Membrane proteins with immunoglobulin-like domains – a master superfamily of interaction molecules”. Semin Immunol 15 (4): 215–223. doi:10.1016/S1044-5323(03)00047-2PMID 14690046.
  21. ^ Putnam FW, Liu YS, Low TL (1979). “Primary structure of a human IgA1 immunoglobulin. IV. Streptococcal IgA1 protease, digestion, Fab and Fc fragments, and the complete amino acid sequence of the alpha 1 heavy chain”. J Biol Chem 254 (8): 2865–74. PMID 107164.
  22. ^ Al-Lazikani B, Lesk AM, Chothia C (1997). “Standard conformations for the canonical structures of immunoglobulins”. J Mol Biol 273 (4): 927–948. doi:10.1006/jmbi.1997.1354.PMID 9367782.
  23. ^ North B, Lehmann A, Dunbrack RL (2010). “A new clustering of antibody CDR loop conformations”J Mol Biol 406 (2): 228–256. doi:10.1016/j.jmb.2010.10.030.PMC 3065967PMID 21035459.
  24. ^ Heyman B (1996). “Complement and Fc-receptors in regulation of the antibody response”.Immunol Lett 54 (2–3): 195–199. doi:10.1016/S0165-2478(96)02672-7PMID 9052877.
  25. ^ Borghesi L, Milcarek C (2006). “From B cell to plasma cell: regulation of V(D)J recombination and antibody secretion”. Immunol Res 36 (1–3): 27–32. doi:10.1385/IR:36:1:27.PMID 17337763.
  26. a b Ravetch J, Bolland S (2001). “IgG Fc receptors”. Annu Rev Immunol 19 (1): 275–290.doi:10.1146/annurev.immunol.19.1.275PMID 11244038.
  27. ^ Rus H, Cudrici C, Niculescu F (2005). “The role of the complement system in innate immunity”. Immunol Res 33 (2): 103–112. doi:10.1385/IR:33:2:103PMID 16234578.
  28. ^ Racaniello, Vincent (2009-10-06). “Natural antibody protects against viral infection”.Virology BlogArchived from the original on 2010-11-17. Retrieved 2010-01-22.
  29. ^ Milland J, Sandrin MS (December 2006). “ABO blood group and related antigens, natural antibodies and transplantation”. Tissue Antigens 68 (6): 459–466. doi:10.1111/j.1399-0039.2006.00721.xPMID 17176435.
  30. ^ Mian I, Bradwell A, Olson A (1991). “Structure, function and properties of antibody binding sites”. J Mol Biol 217 (1): 133–151. doi:10.1016/0022-2836(91)90617-FPMID 1988675.
  31. ^ Fanning LJ, Connor AM, Wu GE (1996). “Development of the immunoglobulin repertoire”.Clin. Immunol. Immunopathol. 79 (1): 1–14. doi:10.1006/clin.1996.0044PMID 8612345.
  32. a b Nemazee D (2006). “Receptor editing in lymphocyte development and central tolerance”.Nat Rev Immunol 6 (10): 728–740. doi:10.1038/nri1939PMID 16998507.
  33. ^ Peter Parham. “The Immune System. 2nd ed. Garland Science: New York, 2005. pg.47-62
  34. ^ Mraz, M.; Dolezalova, D.; Plevova, K.; Stano Kozubik, K.; Mayerova, V.; Cerna, K.; Musilova, K.; Tichy, B. et al. (2012). “MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia”. Blood 119 (9): 2110–2113. doi:10.1182/blood-2011-11-394874PMID 22234685edit
  35. ^ Bergman Y, Cedar H (2004). “A stepwise epigenetic process controls immunoglobulin allelic exclusion”. Nat Rev Immunol 4 (10): 753–761. doi:10.1038/nri1458PMID 15459667.
  36. ^ Honjo T, Habu S (1985). “Origin of immune diversity: genetic variation and selection”. Annu Rev Biochem 54 (1): 803–830. doi:10.1146/ 3927822.
  37. a b Or-Guil M, Wittenbrink N, Weiser AA, Schuchhardt J (2007). “Recirculation of germinal center B cells: a multilevel selection strategy for antibody maturation”. Immunol. Rev. 216: 130–41. doi:10.1111/j.1600-065X.2007.00507.xPMID 17367339.
  38. ^ Neuberger M, Ehrenstein M, Rada C, Sale J, Batista F, Williams G, Milstein C (March 2000).“Memory in the B-cell compartment: antibody affinity maturation”Philos Trans R Soc Lond B Biol Sci 355 (1395): 357–360. doi:10.1098/rstb.2000.0573PMC 1692737.PMID 10794054.
  39. ^ Stavnezer J, Amemiya CT (2004). “Evolution of isotype switching”. Semin. Immunol. 16 (4): 257–275. doi:10.1016/j.smim.2004.08.005PMID 15522624.
  40. ^ Durandy A (2003). “Activation-induced cytidine deaminase: a dual role in class-switch recombination and somatic hypermutation”. Eur. J. Immunol. 33 (8): 2069–2073.doi:10.1002/eji.200324133PMID 12884279.
  41. ^ Casali P, Zan H (2004). “Class switching and Myc translocation: how does DNA break?”. Nat. Immunol. 5 (11): 1101–1103. doi:10.1038/ni1104-1101PMID 15496946.
  42. ^ Lieber MR, Yu K, Raghavan SC (2006). “Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocations”. DNA Repair (Amst.) 5 (9–10): 1234–1245. doi:10.1016/j.dnarep.2006.05.013PMID 16793349.
  43. ^ page 22 in: Shoenfeld, Yehuda.; Meroni, Pier-Luigi.; Gershwin, M. Eric (2007).Autoantibodie. Amsterdam ; Boston: Elsevier. ISBN 978-0-444-52763-9.
  44. a b Farlex dictionary > monovalent Citing: The American Heritage Science Dictionary, Copyright 2005
  45. a b Farlex dictionary > polyvalent Citing: The American Heritage Medical Dictionary. 2004
  46. ^ “Animated depictions of how antibodies are used in ELISA assays”. Cellular Technology Ltd.—EuropeArchived from the original on 2010-11-17. Retrieved 2007-05-08.
  47. ^ “Animated depictions of how antibodies are used in ELISPOT assays”. Cellular Technology Ltd.—EuropeArchived from the original on 2010-11-17. Retrieved 2007-05-08.
  48. ^ Stern P (2006). “Current possibilities of turbidimetry and nephelometry”Klin Biochem Metab 14 (3): 146–151. Archived from the original on 2010-11-17.
  49. a b Dean, Laura (2005). “Chapter 4: Hemolytic disease of the newborn”Blood Groups and Red Cell Antigens. NCBI Bethesda (MD): National Library of Medicine (US),.
  50. ^ Feldmann M, Maini R (2001). “Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?”. Annu Rev Immunol 19 (1): 163–196. doi:10.1146/annurev.immunol.19.1.163.PMID 11244034.
  51. ^ Doggrell S (2003). “Is natalizumab a breakthrough in the treatment of multiple sclerosis?”.Expert Opin Pharmacother 4 (6): 999–1001. doi:10.1517/14656566.4.6.999.PMID 12783595.
  52. ^ Krueger G, Langley R, Leonardi C, Yeilding N, Guzzo C, Wang Y, Dooley L, Lebwohl M (2007). “A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis”. N Engl J Med356 (6): 580–592. doi:10.1056/NEJMoa062382PMID 17287478.
  53. ^ Plosker G, Figgitt D (2003). “Rituximab: a review of its use in non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia”. Drugs 63 (8): 803–843. doi:10.2165/00003495-200363080-00005PMID 12662126.
  54. ^ Vogel C, Cobleigh M, Tripathy D, Gutheil J, Harris L, Fehrenbacher L, Slamon D, Murphy M, Novotny W, Burchmore M, Shak S, Stewart S (2001). “First-line Herceptin monotherapy in metastatic breast cancer”. Oncology. 61 Suppl 2 (Suppl. 2): 37–42. doi:10.1159/000055400.PMID 11694786.
  55. ^ LeBien TW (1 July 2000). “Fates of human B-cell precursors”Blood 96 (1): 9–23.PMID 10891425Archived from the original on 2010-11-17.
  56. ^ Ghaffer A (2006-03-26). “Immunization”Immunology — Chapter 14. University of South Carolina School of Medicine. Archived from the original on 2010-11-17. Retrieved 2007-06-06.
  57. ^ Urbaniak S, Greiss M (2000). “RhD haemolytic disease of the fetus and the newborn”. Blood Rev 14 (1): 44–61. doi:10.1054/blre.1999.0123PMID 10805260.
  58. a b Fung Kee Fung K, Eason E, Crane J, Armson A, De La Ronde S, Farine D, Keenan-Lindsay L, Leduc L, Reid G, Aerde J, Wilson R, Davies G, Désilets V, Summers A, Wyatt P, Young D (2003). “Prevention of Rh alloimmunization”. J Obstet Gynaecol Can 25 (9): 765–73.PMID 12970812.
  59. ^ Tini M, Jewell UR, Camenisch G, Chilov D, Gassmann M (2002). “Generation and application of chicken egg-yolk antibodies”. Comp. Biochem. Physiol., Part a Mol. Integr. Physiol. 131 (3): 569–574. doi:10.1016/S1095-6433(01)00508-6PMID 11867282.
  60. ^ Cole SP, Campling BG, Atlaw T, Kozbor D, Roder JC (1984). “Human monoclonal antibodies”. Mol. Cell. Biochem. 62 (2): 109–20. doi:10.1007/BF00223301PMID 6087121.
  61. ^ Kabir S (2002). “Immunoglobulin purification by affinity chromatography using protein A mimetic ligands prepared by combinatorial chemical synthesis”. Immunol Invest 31 (3–4): 263–278. doi:10.1081/IMM-120016245PMID 12472184.
  62. a b Brehm-Stecher B, Johnson E (2004). “Single-cell microbiology: tools, technologies, and applications”Microbiol Mol Biol Rev 68 (3): 538–559. doi:10.1128/MMBR.68.3.538-559.2004PMC 515252PMID 15353569Archived from the original on 2010-11-17.
  63. ^ Williams N (2000). “Immunoprecipitation procedures”. Methods Cell Biol. Methods in Cell Biology 62: 449–453. doi:10.1016/S0091-679X(08)61549-6ISBN 978-0-12-544164-3.PMID 10503210.
  64. ^ Kurien B, Scofield R (2006). “Western blotting”. Methods 38 (4): 283–293.doi:10.1016/j.ymeth.2005.11.007PMID 16483794.
  65. ^ Scanziani E (1998). “Immunohistochemical staining of fixed tissues”. Methods Mol Biol 104: 133–140. doi:10.1385/0-89603-525-5:133ISBN 978-0-89603-525-6PMID 9711649.
  66. ^ Reen DJ. (1994). “Enzyme-linked immunosorbent assay (ELISA)”. Methods Mol Biol. 32: 461–466. doi:10.1385/0-89603-268-X:461ISBN 0-89603-268-XPMID 7951745.
  67. ^ Kalyuzhny AE (2005). “Chemistry and biology of the ELISPOT assay”. Methods Mol Biol. 302: 015–032. doi:10.1385/1-59259-903-6:015ISBN 1-59259-903-6PMID 15937343.
  68. ^ Whitelegg N.R.J., Rees A.R. (2000). “WAM: an improved algorithm for modeling antibodies on the WEB”Protein Engineering 13 (12): 819–824. doi:10.1093/protein/13.12.819.PMID 11239080Archived from the original on 2010-11-17.
  69. ^ Marcatili P, Rosi A,Tramontano A (2008). “PIGS: automatic prediction of antibody structures”Bioinformatics 24 (17): 1953–1954. doi:10.1093/bioinformatics/btn341.PMID 18641403Archived from the original on 2010-11-17.
    Prediction of Immunoglobulin Structure (PIGS)
  70. ^ Sivasubramanian A, Sircar A, Chaudhury S, Gray J J (2009). “Toward high-resolution homology modeling of antibody Fv regions and application to antibody–antigen docking”.Proteins 74 (2): 497–514. doi:10.1002/prot.22309PMC 2909601PMID 19062174.Archived from the original on 2010-11-17.
  71. a b c Lindenmann, Jean (1984). “Origin of the Terms ‘Antibody’ and ‘Antigen'”Scand. J. Immunol. 19 (4): 281–5. doi:10.1111/j.1365-3083.1984.tb00931.xPMID 6374880.Archived from the original on 2010-11-17. Retrieved 2008-11-01.
  72. ^ Padlan, Eduardo (February 1994). “Anatomy of the antibody molecule”. Mol. Immunol. 31 (3): 169–217. doi:10.1016/0161-5890(94)90001-9PMID 8114766.
  73. ^ “New Sculpture Portraying Human Antibody as Protective Angel Installed on Scripps Florida Campus”Archived from the original on 2010-11-17. Retrieved 2008-12-12.
  74. ^ “Protein sculpture inspired by Vitruvian Man”Archived from the original on 2010-11-17. Retrieved 2008-12-12.
  75. ^ “Emil von Behring — Biography”Archived from the original on 2010-11-17. Retrieved 2007-06-05.
  76. ^ AGN (1931). “The Late Baron Shibasaburo Kitasato”Canadian Medical Association Journal 25 (2): 206. PMC 382621PMID 20318414.
  77. ^ Winau F, Westphal O, Winau R (2004). “Paul Ehrlich–in search of the magic bullet”. Microbes Infect. 6 (8): 786–789. doi:10.1016/j.micinf.2004.04.003PMID 15207826.
  78. ^ Silverstein AM (2003). “Cellular versus humoral immunology: a century-long dispute”. Nat. Immunol. 4 (5): 425–428. doi:10.1038/ni0503-425PMID 12719732.
  79. ^ Van Epps HL (2006). “Michael Heidelberger and the demystification of antibodies”J. Exp. Med. 203 (1): 5. doi:10.1084/jem.2031ftaPMC 2118068PMID 16523537Archivedfrom the original on 2010-11-17.
  80. ^ Marrack, JR (1938). Chemistry of antigens and antibodies (2nd ed.). London: His Majesty’s Stationery Office. OCLC 3220539.
  81. ^ “The Linus Pauling Papers: How Antibodies and Enzymes Work”Archived from the original on 2010-11-17. Retrieved 2007-06-05.
  82. ^ Silverstein AM (2004). “Labeled antigens and antibodies: the evolution of magic markers and magic bullets”Nat. Immunol. 5 (12): 1211–1217. doi:10.1038/ni1140PMID 15549122.Archived from the original on 2009-12-18.
  83. ^ Edelman GM, Gally JA (1962). “The nature of Bence-Jones proteins. Chemical similarities to polypetide chains of myeloma globulins and normal gamma-globulins”J. Exp. Med. 116 (2): 207–227. doi:10.1084/jem.116.2.207PMC 2137388PMID 13889153.
  84. ^ Stevens FJ, Solomon A, Schiffer M (1991). “Bence Jones proteins: a powerful tool for the fundamental study of protein chemistry and pathophysiology”. Biochemistry 30 (28): 6803–6805. doi:10.1021/bi00242a001PMID 2069946.
  85. a b Raju TN (1999). “The Nobel chronicles. 1972: Gerald M Edelman (b 1929) and Rodney R Porter (1917-85)”. Lancet 354 (9183): 1040. doi:10.1016/S0140-6736(05)76658-7.PMID 10501404.
  86. ^ Hochman J, Inbar D, Givol D (1973). “An active antibody fragment (Fv) composed of the variable portions of heavy and light chains”. Biochemistry 12 (6): 1130–1135.doi:10.1021/bi00730a018PMID 4569769.
  87. ^ Tomasi TB (1992). “The discovery of secretory IgA and the mucosal immune system”.Immunol. Today 13 (10): 416–418. doi:10.1016/0167-5699(92)90093-MPMID 1343085.
  88. ^ Preud’homme JL, Petit I, Barra A, Morel F, Lecron JC, Lelièvre E (2000). “Structural and functional properties of membrane and secreted IgD”. Mol. Immunol. 37 (15): 871–887.doi:10.1016/S0161-5890(01)00006-2PMID 11282392.
  89. ^ Johansson SG (2006). “The discovery of immunoglobulin E”. Allergy and asthma proceedings : the official journal of regional and state allergy societies 27 (2 Suppl 1): S3–6.PMID 16722325.
  90. ^ Hozumi N, Tonegawa S (1976). “Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions”Proc. Natl. Acad. Sci. U.S.A. 73 (10): 3628–3632. doi:10.1073/pnas.73.10.3628PMC 431171PMID 824647.

External links

Wikimedia Commons has media related to: Antibodies