The immunoglobulin light chain is the small polypeptide subunit of an antibody (immunoglobulin).
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A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two Ig light chains.
The immunoglobulin light chain is the small polypeptide subunit of an antibody (immunoglobulin).
A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two Ig light chains.
There are two types of light chain in humans:
Antibodies are produced by B lymphocytes, each expressing only one class of light chain. Once set, light chain class remains fixed for the life of the B lymphocyte. In a healthy individual, the total kappa-to-lambda ratio is roughly 2:1 in serum (measuring intact whole antibodies) or 1:1.5 if measuring free light chains, with a highly divergent ratio indicative of neoplasm. The free light chain ratio ranges from 0.26 to 1.65. [1] Both the kappa and the lambda chains can increase proportionately, maintaining a normal ratio. This is usually indicative of something other than a blood cell dyscrasia, such as kidney disease.
The immunoglobulin light chain genes in tetrapods can be classified into three distinct groups: kappa (κ), lambda (λ), and sigma (σ). The divergence of the κ, λ, and σ isotypes preceded the radiation of tetrapods. The σ isotype was lost after the evolution of the amphibian lineage and before the emergence of the reptilian lineage. [2]
Other types of light chains can be found in lower vertebrates, such as the Ig-Light-Iota chain of Chondrichthyes and Teleostei. [3] [4]
Camelids are unique among mammals as they also have fully functional antibodies which have two heavy chains, but lack the light chains usually paired with each heavy chain. [5]
Sharks also possess, as part of their adaptive immune systems, a functional heavy-chain homodimeric antibody-like molecule referred to as IgNAR (immunoglobulin new antigen receptor). IgNAR is believed to have never had an associated light chain, in contrast with the understanding that the heavy-chain-only antibodies in camelids may have lost their light chain partners through evolution. [6] [7]
Only one type of light chain is present in a typical antibody, thus the two light chains of an individual antibody are identical.
Each light chain is composed of two tandem immunoglobulin domains:
The approximate length of a light chain protein is from 211 to 217 amino acids. [3] The constant region determines what class (kappa or lambda) the light chain is. [8] The lambda class has 4 subtypes (1, 2, 3, and 7). [8]
Individual B-cells in lymphoid tissue possess either kappa or lambda light chains, but never both together. Using immunohistochemistry, it is possible to determine the relative abundance of B-cells expressing kappa and lambda light chains. If the lymph node or similar tissue is reactive, or otherwise benign, it should possess a mixture of kappa positive and lambda positive cells. If, however, one type of light chain is significantly more common than the other, the cells are likely all derived from a small clonal population, which may indicate a malignant condition, such as B-cell lymphoma. [9]
Free immunoglobulin light chains secreted by neoplastic plasma cells, such as in multiple myeloma, can be called Bence Jones protein when detected in the urine, although there is a trend to refer to these as urinary free light chains.
Increased levels of free Ig light chains have also been detected in various inflammatory diseases. It is important to note that, in contrast to increased levels in lymphoma patients, these Ig light chains are polyclonal. Recent studies have shown that these Ig light chains can bind to mast cells and, using their ability to bind antigen, facilitate activation of these mast cells. [10] Activation of mast cells results in the release of various pro-inflammatory mediators which are believed to contribute to the development of the inflammatory disease. Recent studies have shown that Ig light chains not only activate mast cells but also dorsal root ganglia [11] and neutrophils, [12] expanding their possible role as mediators in inflammatory disease.
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope 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 it directly.
Immunoglobulin G is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG antibody has two paratopes.
Immunoglobulin D (IgD) is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually co-expressed with another cell surface antibody called IgM. IgD is also produced in a secreted form that is found in very small amounts in blood serum, representing 0.25% of immunoglobulins in serum. The relative molecular mass and half-life of secreted IgD is 185 kDa and 2.8 days, respectively. Secreted IgD is produced as a monomeric antibody with two heavy chains of the delta (δ) class, and two Ig light chains.
Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.
Immunoglobulin M (IgM) is one of several isotypes of antibody that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antigen. In humans and other mammals that have been studied, plasmablasts residing in the spleen are the main source for specific IgM production.
Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins that become insoluble at reduced temperatures. This should be contrasted with cold agglutinins, which cause agglutination of red blood cells.
The immunoglobulin heavy chain (IgH) is the large polypeptide subunit of an antibody (immunoglobulin). In human genome, the IgH gene loci are on chromosome 14.
V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively. The process is a defining feature of the adaptive immune system.
The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, and is typically located on the outer surface of these lymphocyte cells. Through biochemical signaling and by physically acquiring antigens from the immune synapses, the BCR controls the activation of the B cell. B cells are able to gather and grab antigens by engaging biochemical modules for receptor clustering, cell spreading, generation of pulling forces, and receptor transport, which eventually culminates in endocytosis and antigen presentation. B cells' mechanical activity adheres to a pattern of negative and positive feedbacks that regulate the quantity of removed antigen by manipulating the dynamic of BCR–antigen bonds directly. Particularly, grouping and spreading increase the relation of antigen with BCR, thereby proving sensitivity and amplification. On the other hand, pulling forces delinks the antigen from the BCR, thus testing the quality of antigen binding.
Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination (CSR), is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the isotype IgM to the isotype IgG. During this process, the constant-region portion of the antibody heavy chain is changed, but the variable region of the heavy chain stays the same. Since the variable region does not change, class switching does not affect antigen specificity. Instead, the antibody retains affinity for the same antigens, but can interact with different effector molecules.
The word allotype comes from two Greek roots, allo meaning 'other or differing from the norm' and typos meaning 'mark'. In immunology, allotype is an immunoglobulin variation that can be found among antibody classes and is manifested by heterogeneity of immunoglobulins present in a single vertebrate species. The structure of immunoglobulin polypeptide chain is dictated and controlled by number of genes encoded in the germ line. However, these genes, as it was discovered by serologic and chemical methods, could be highly polymorphic. This polymorphism is subsequently projected to the overall amino acid structure of antibody chains. Polymorphic epitopes can be present on immunoglobulin constant regions on both heavy and light chains, differing between individuals or ethnic groups and in some cases may pose as immunogenic determinants. Exposure of individuals to a non-self allotype might elicit an anti- allotype response and became cause of problems for example in a patient after transfusion of blood or in a pregnant woman. However, it is important to mention that not all variations in immunoglobulin amino acid sequence pose as a determinant responsible for immune response. Some of these allotypic determinants may be present at places that are not well exposed and therefore can be hardly serologically discriminated. In other cases, variation in one isotype can be compensated by the presence of this determinant on another antibody isotype in one individual. This means that divergent allotype of heavy chain of IgG antibody may be balanced by presence of this allotype on heavy chain of for example IgA antibody and therefore is called isoallotypic variant. Especially large number of polymorphisms were discovered in IgG antibody subclasses. Which were practically used in forensic medicine and in paternity testing, before replaced by modern day DNA fingerprinting.
In immunology, antibodies are classified into several types called isotypes or classes. The variable (V) regions near the tip of the antibody can differ from molecule to molecule in countless ways, allowing it to specifically target an antigen . In contrast, the constant (C) regions only occur in a few variants, which define the antibody's class. Antibodies of different classes activate distinct effector mechanisms in response to an antigen . They appear at different stages of an immune response, differ in structural features, and in their location around the body.
Protein L was first isolated from the surface of bacterial species Peptostreptococcus magnus and was found to bind immunoglobulins through L chain interaction, from which the name was suggested. It consists of 719 amino acid residues. The molecular weight of Protein L purified from the cell walls of Peptostreptoccus magnus was first estimated as 95kD by SDS-PAGE in the presence of reducing agent 2-mercaptoethanol, while the molecular weight was determined to 76kD by gel chromotography in the presence of 6 M guanidine HCl. Protein L does not contain any interchain disulfide loops, nor does it consist of disulfide-linked subunits. It is an acidic molecule with a pI of 4.0. Unlike Protein A and Protein G, which bind to the Fc region of immunoglobulins (antibodies), Protein L binds antibodies through light chain interactions. Since no part of the heavy chain is involved in the binding interaction, Protein L binds a wider range of antibody classes than Protein A or G. Protein L binds to representatives of all antibody classes, including IgG, IgM, IgA, IgE and IgD. Single chain variable fragments (scFv) and Fab fragments also bind to Protein L.
Immunoglobulin lambda-like polypeptide 1 is a protein that in humans is encoded by the IGLL1 gene. IGLL1 has also recently been designated CD179B.
Immunoglobulin lambda locus, also known as IGL@, is a region on the q arm of human chromosome 22, region 11.22 (22q11.22) that contains genes for the lambda light chains of antibodies.
Immunoglobulin kappa locus, also known as IGK@, is a region on the p arm of human chromosome 2, region 11.2 (2p11.2), that contains genes for the kappa (κ) light chains of antibodies.
Plasma cell dyscrasias are a spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells over-produce and secrete into the blood stream a myeloma protein, i.e. an abnormal monoclonal antibody or portion thereof. The exception to this rule is the disorder termed non-secretory multiple myeloma; this disorder is a form of plasma cell dyscrasia in which no myeloma protein is detected in serum or urine of individuals who have clear evidence of an increase in clonal bone marrow plasma cells and/or evidence of clonal plasma cell-mediated tissue injury. Here, a clone of plasma cells refers to group of plasma cells that are abnormal in that they have an identical genetic identity and therefore are descendants of a single genetically distinct ancestor cell.
A heavy-chain antibody is an antibody which consists only of two heavy chains and lacks the two light chains usually found in antibodies.
Antibody structure is made up of two heavy-chains and two light-chains. These chains are held together by disulfide bonds. The arrangement or processes that put together different parts of this antibody molecule play important role in antibody diversity and production of different subclasses or classes of antibodies. The organization and processes take place during the development and differentiation of B cells. That is, the controlled gene expression during transcription and translation coupled with the rearrangements of immunoglobulin gene segments result in the generation of antibody repertoire during development and maturation of B cells.
Anti-immunoglobulin antibodies are defined as a protein that detects other antibodies from an organism. Specifically, anti-immunoglobulin antibodies are created by B-cells as antibodies to bind to other immunoglobulins. Immunoglobulins have two regions: the constant region and the variable region. The constant region is involved in effector function, while the variable region is involved in recognizing and binding to antigens. Anti-immunoglobulin antibodies may bind to either the variable or constant region of the immunoglobulin. Anti-immunoglobulin antibodies are a type of secondary antibody. They are able to detect primary antibodies through multiple methods such as a Western blot, immunohistochemistry, immunofluorescence staining, flow cytometry, and ELISA.
