Alternative titles; symbols
Cytogenetic location: 2p12 Genomic coordinates (GRCh38): 2:74,800,001-83,100,000
Immunoglobulins (Ig) are the antigen recognition molecules of B cells. An Ig molecule is made up of 2 identical heavy chains (see 147100) and 2 identical light chains, either kappa or lambda (see 147220), joined by disulfide bonds so that each heavy chain is linked to a light chain and the 2 heavy chains are linked together. The kappa and lambda light chains have no apparent functional differences. Each Ig kappa light chain has an N-terminal variable (V) region containing the antigen-binding site and a C-terminal constant (C) region, encoded by a C region gene (IGKC; 147200), that provides signaling functions. The kappa light chain V region is encoded by 2 types of genes: V genes and joining (J) genes (see 146970). Random selection of just 1 gene of each type to assemble a V region accounts for the great diversity of V regions among Ig molecules. The kappa light chain locus on chromosome 2 contains approximately 40 functional V genes, followed by approximately 5 functional J genes. Due to polymorphism, the numbers of functional V and J genes differ among individuals (Janeway et al., 2005).
Four subgroups of the variable region of kappa light chains are recognized: Vk I, Vk II, Vk III, and Vk IV. They are, presumably, determined by separate but closely linked loci. Bentley and Rabbitts (1981) concluded that there are 15 to 20 kappa variable region genes in man.
The kappa variable genes number more than 25 and less than 50, in all. There is only one germline V(K)IV gene (Klobeck et al., 1985; Marsh et al., 1985).
The Ig kappa light chain V gene cluster is located within the Ig kappa light chain locus on chromosome 2p12 (Malcolm et al., 1982).
Leong et al. (1984) isolated metaphase chromosomes from human lymphocytes, stained them with ethidium bromide, and sorted them with a fluorescence-activated sorter. DNA from the sorted chromosomes was denatured and spotted directly onto nitrocellulose filters. A nick-translated human variable region kappa light chain gene probe was then hybridized to the spots. By this so-called dot hybridization, the kappa variable gene probe was found to hybridize only with the sorted chromosome fraction containing chromosomes 1 and 2.
Lotscher et al. (1986) mapped an IGKV pseudogene (IGKVP1) to 1p13-q12, another (IGKVP2) to chromosome 15, and a cluster of 3 (IGKVP3, 4, and 5) to chromosome 22.
Allelic exclusion ensures monoallelic expression of Ig genes by each B cell to maintain single receptor specificity. Using FISH analysis for DNA replication timing in mouse spleen cells, Mostoslavsky et al. (2001) showed that IGKC, IGKV, and IGHM (147020), as well as TCRB (see 186930), replicate asynchronously, indicated by a high frequency of single (pre-replication) and double (after replication) hybridization signals in the loci of interphase nuclei, in a manner analogous to the process of X chromosome inactivation. Mostoslavsky et al. (2001) concluded that monoallelic inactivation is not unique to the X chromosome, but can also take place, in a regional manner, on autosomes as well. They noted that asynchronous replication also occurs at the loci for olfactory receptors (see OR2H3, 600578), IL2 (147680), and IL4 (147780).
Skok et al. (2001) used FISH analysis and multicolor fluorescence microscopy to demonstrate that after activation of mature B cells, a single endogenous IGHM allele, as well as 3 IGL (see IGLC1, 147220) alleles, are recruited to centromeric heterochromatin containing Ikaros (603023), a protein required for B and T lymphocyte development and implicated in the silencing of specific target genes, whereas the other IGHM and IGK alleles are localized away from centromeric heterochromatin. Skok et al. (2001) concluded that epigenetic factors may have a role in maintaining the monoallelic expression of Ig in normal B cells.
Emanuel et al. (1984) found that the 2p breakpoint in a Burkitt lymphoma cell line carrying a 2;8 translocation was in the distal portion of 2p11.2. Specifically, the kappa variable genes were involved at the break site.
Bentley, D. L., Rabbitts, T. H. Evolution of immunoglobulin V genes: evidence indicating that recently duplicated human V(kappa) sequences have diverged by gene conversion. Cell 32: 181-189, 1983. [PubMed: 6402305] [Full Text: https://doi.org/10.1016/0092-8674(83)90508-1]
Bentley, D. L., Rabbitts, T. H. Human V(kappa) immunoglobulin gene number: implications for the origin of antibody diversity. Cell 24: 613-623, 1981. [PubMed: 6265099] [Full Text: https://doi.org/10.1016/0092-8674(81)90088-x]
Emanuel, B. S., Selden, J. R., Chaganti, R. S. K., Jhanwar, S., Nowell, P. C., Croce, C. M. The 2p breakpoint of a 2;8 translocation in Burkitt lymphoma interrupts the V(kappa) locus. Proc. Nat. Acad. Sci. 81: 2444-2446, 1984. [PubMed: 6585808] [Full Text: https://doi.org/10.1073/pnas.81.8.2444]
Janeway, C. A., Jr., Travers, P., Walport, M., Shlomchik, M. J. Immunobiology: The Immune System in Health and Disease. (6th ed.) New York: Garland Science Publishing (pub.) 2005. Pp. 103-106, and 135-139.
Klobeck, H.-G., Bornkamm, G. W., Combriato, G., Mocikat, R., Pohlenz, H.-D., Zachau, H. G. Subgroup IV of human immunoglobulin K light chains is encoded by a single germline gene. Nucleic Acids Res. 13: 6515-6529, 1985. [PubMed: 2997712] [Full Text: https://doi.org/10.1093/nar/13.18.6515]
Klobeck, H.-G., Meindl, A., Combriato, G., Solomon, A., Zachau, H. G. Human immunoglobulin kappa light chain genes of subgroups II and III. Nucleic Acids Res. 13: 6499-6513, 1985. [PubMed: 2997711] [Full Text: https://doi.org/10.1093/nar/13.18.6499]
Leong, M. M. L., Gilmore, D., Milstein, C. Gene mapping of sorted chromosomes by dot hybridization. (Abstract) Cytogenet. Cell Genet. 37: 522 only, 1984.
Lotscher, E., Grzeschik, K.-H., Bauer, H. G., Pohlenz, H.-D., Straubinger, B., Zachau, H. G. Dispersed human immunoglobulin kappa light-chain genes. Nature 320: 456-458, 1986. [PubMed: 3083265] [Full Text: https://doi.org/10.1038/320456a0]
Malcolm, S., Barton, P., Ferguson-Smith, M. A., Bentley, D. L., Rabbitts, T. H. Localization of human immunoglobulin kappa light chain variable region genes to the short arm of chromosome 2 by in situ hybridization. Proc. Nat. Acad. Sci. 79: 4957-4961, 1982. [PubMed: 6812058] [Full Text: https://doi.org/10.1073/pnas.79.16.4957]
Marsh, P., Mills, F., Gould, H. Detection of a unique human V(kappa)IV germline gene by a cloned cDNA probe. Nucleic Acids Res. 13: 6531-6544, 1985. [PubMed: 2997713] [Full Text: https://doi.org/10.1093/nar/13.18.6531]
Mostoslavsky, R., Singh, N., Tenzen, T., Goldmit, M., Gabay, C., Elizur, S., Qi, P., Reubinoff, B. E., Chess, A., Cedar, H., Bergman, Y. Asynchronous replication and allelic exclusion in the immune system. Nature 414: 221-225, 2001. [PubMed: 11700561] [Full Text: https://doi.org/10.1038/35102606]
Skok, J. A., Brown, K. E., Azuara, V., Caparros, M. L., Baxter, J., Takacs, K., Dillon, N., Gray, D., Perry, R. P., Merkenschlager, M., Fisher, A. G. Nonequivalent nuclear location of immunoglobulin alleles in B lymphocytes. Nature Immun. 2: 848-54, 2001. [PubMed: 11526401] [Full Text: https://doi.org/10.1038/ni0901-848]
Straubinger, B., Huber, E., Lorenz, W., Osterholzer, E., Pargent, W., Pech, M., Pohlenz, H.-D., Zimmer, F.-J., Zachau, H. G. The human V(K) locus: characterization of a duplicated region encoding 28 different immunoglobulin genes. J. Molec. Biol. 199: 23-34, 1988. [PubMed: 3351922] [Full Text: https://doi.org/10.1016/0022-2836(88)90376-2]