Immunoglobulin light chain
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 (as in other mammals),
- kappa (κ) chain, encoded by the immunoglobulin kappa locus (IGK@) on chromosome 2
- lambda (λ) chain, encoded by the immunoglobulin lambda locus (IGL@) on chromosome 22
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 3:1 in serum (measuring intact whole antibodies) or 1:1.5 if measuring free light chains, with a highly divergent ratio indicative of neoplasm.
The exact normal ratio of kappa to lambda, according to a novel polyclonal free light chain assay, ranges from 0.26 to 1.65. 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.
In other animals
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.
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. The functional role of this separate repertoire is unknown as yet.
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:
- one constant (CL) domain
- one variable domain (VL) that is important for binding antigen
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.
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 (Redegeld (2002)). 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 (Rijnierse, 2009)) and neutrophils (Braber and Thio (2012)), expanding their possible role as mediators in inflammatory disease.
- Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA (2001). "Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains". Clin Chem 48 (9): 1437–44. PMID 12194920.
- Das S, Nikolaidis N, Klein J, Nei M (2008). "Evolutionary redefinition of immunoglobulin light chain isotypes in tetrapods using molecular markers". Proc Natl Acad Sci U S A. 105 (43): 16647–52. doi:10.1073/pnas.0808800105. PMC 2575474. PMID 18940927.
- Janeway CA, Jr. et al. (2001). Immunobiology. (5th ed.). Garland Publishing. (electronic full text via NCBI Bookshelf) ISBN 0-8153-3642-X.
- IMGT Index Antibodies (or Immunoglobulins).
- Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hamers C, Songa E, Bendahman N, Hamers R (1993). "Naturally occurring antibodies devoid of light chains". Nature 363 (6428): 446–8. doi:10.1038/363446a0. PMID 8502296.
- Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 283–285. ISBN 1-84110-100-1.
- Immunoglobulin Light Chains at the US National Library of Medicine Medical Subject Headings (MeSH)
- Educational Resource for Immunoglobulin Light Chains