Abstract
Mutations in immunoglobulin V-genes can be due to gene multiplication, allelic variations, mutations induced by antigens or somatic mutations, etc., and various combinations of these. Since the number of different mouse lambda light V-gene nucleotide sequences is relatively small, a pairwise comparison between these sequences can provide a rough idea as to the contributions of the above mechanisms to the number of nucleotide differences between sequences. A plot of occurrences against the number of differences suggests that differences between one to five can be attributed to somatic mutations. Six to 12 differences can be allelic. Thirteen to 17 may be due to allelic variations together with somatic mutations. Differences >17 appear to be derived from gene multiplication. Although these numbers are most likely somewhat different in humans, they can nevertheless provide a rough guide to sort out the effect of gene multiplication. Estimations of human heavy, kappa and lambda light chain immunoglobulin V-genes are in reasonably good agreement with recent experimental studies. For mouse kappa light and heavy chains, our estimations can provide some insight to future analyses by direct sequencing of these gene segments.
Full Text
The Full Text of this article is available as a PDF (771.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baldwin E., Schultz P. G. Generation of a catalytic antibody by site-directed mutagenesis. Science. 1989 Sep 8;245(4922):1104–1107. doi: 10.1126/science.2672338. [DOI] [PubMed] [Google Scholar]
- Baltimore D. Gene conversion: some implications for immunoglobulin genes. Cell. 1981 Jun;24(3):592–594. doi: 10.1016/0092-8674(81)90082-9. [DOI] [PubMed] [Google Scholar]
- Ch'ang L. Y., Schell M., Ringelberg C., Weiss D. T., Solomon A. Molecular characterization of a human V lambda VIII germline gene. Mol Immunol. 1995 Jan;32(1):49–55. doi: 10.1016/0161-5890(94)00135-n. [DOI] [PubMed] [Google Scholar]
- Chen C., Roberts V. A., Rittenberg M. B. Generation and analysis of random point mutations in an antibody CDR2 sequence: many mutated antibodies lose their ability to bind antigen. J Exp Med. 1992 Sep 1;176(3):855–866. doi: 10.1084/jem.176.3.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frippiat J. P., Williams S. C., Tomlinson I. M., Cook G. P., Cherif D., Le Paslier D., Collins J. E., Dunham I., Winter G., Lefranc M. P. Organization of the human immunoglobulin lambda light-chain locus on chromosome 22q11.2. Hum Mol Genet. 1995 Jun;4(6):983–991. doi: 10.1093/hmg/4.6.983. [DOI] [PubMed] [Google Scholar]
- Kirschbaum T., Jaenichen R., Zachau H. G. The mouse immunoglobulin kappa locus contains about 140 variable gene segments. Eur J Immunol. 1996 Jul;26(7):1613–1620. doi: 10.1002/eji.1830260731. [DOI] [PubMed] [Google Scholar]
- Milstein C. Linked groups of residues in immunoglobulin k chains. Nature. 1967 Oct 28;216(5113):330–332. doi: 10.1038/216330a0. [DOI] [PubMed] [Google Scholar]
- Motoyama N., Miwa T., Suzuki Y., Okada H., Azuma T. Comparison of somatic mutation frequency among immunoglobulin genes. J Exp Med. 1994 Feb 1;179(2):395–403. doi: 10.1084/jem.179.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Motoyama N., Okada H., Azuma T. Somatic mutation in constant regions of mouse lambda 1 light chains. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7933–7937. doi: 10.1073/pnas.88.18.7933. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Potter M. Antigen-binding myeloma proteins of mice. Adv Immunol. 1977;25:141–211. [PubMed] [Google Scholar]
- Reidl L. S., Kinoshita C. M., Steiner L. A. Wild mice express an Ig V lambda gene that differs from any V lambda in BALB/c but resembles a human V lambda subgroup. J Immunol. 1992 Jul 15;149(2):471–480. [PubMed] [Google Scholar]
- Reynaud C. A., Anquez V., Dahan A., Weill J. C. A single rearrangement event generates most of the chicken immunoglobulin light chain diversity. Cell. 1985 Feb;40(2):283–291. doi: 10.1016/0092-8674(85)90142-4. [DOI] [PubMed] [Google Scholar]
- Reynaud C. A., Dahan A., Anquez V., Weill J. C. Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region. Cell. 1989 Oct 6;59(1):171–183. doi: 10.1016/0092-8674(89)90879-9. [DOI] [PubMed] [Google Scholar]
- Sanchez P., Marche P. N., Le Guern C., Cazenave P. A. Structure of a third murine immunoglobulin lambda light chain variable region that is expressed in laboratory mice. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9185–9188. doi: 10.1073/pnas.84.24.9185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanchez P., Marche P. N., Rueff-Juy D., Cazenave P. A. Mouse V lambda x gene sequence generates no junctional diversity and is conserved in mammalian species. J Immunol. 1990 Apr 1;144(7):2816–2820. [PubMed] [Google Scholar]