Abstract
Studies of the murine λ1 light chains produced by myeloma cells provided the first evidence for somatic point mutation of germ-line variable (V) region genes. An examination of the variable regions of 19 λ1 chains revealed seven which differed from a common sequence by one to three amino acid substitutions1. Subsequently, one of these presumed somatic variants of the single λ1 V gene was characterized by DNA sequence analysis of the rearranged functional gene2. The predicted DNA sequence alteration was observed and no silent mutation was evident. These studies of λ chain variants suggested that the hypervariable, complementarity-determining regions (CDRs) ht be a preferred site of somatic mutation because all seven characterized variants contained substitutions only in these regions. By contrast, comparisons of closely related κ chain variable region amino acid sequences, and more recently Vκ and VH genes8–12, have suggested that somatic mutation probably occurs in codons for both framework and CDR residues. To examine this apparent discrepancy between the sites of somatic mutation in λ and κ genes, we have determined the nucleotide sequence of two λ 1 gene from hybridomas and a λ 2 gene from a myeloma. These sequences demonstrate that somatic mutation in λ genes can occur in both the framework and CDR residues.
Similar content being viewed by others
References
Weigert, M. & Riblet, R. Cold Spring Harb Symp. quant. Biol. 41, 837–846 (1976).
Bernard, O., Hozumi, N. & Tonegawa, S. Cell 15, 1133–1144 (1978).
Weigert, M., Gatmaitan, L., Loh, E., Schilling, J. & Hood, L. Nature 276, 785–790 (1978).
Valbuena, O., Marcu, K. B., Weigert, M. & Perry, R. Nature 276, 780–784 (1978).
Pech, M., Hochtl, J., Schnell, H. & Zachau, H. G. Nature 291, 668–670 (1981).
Selsing, E. & Storb, U. Cell 25, 47–58 (1981).
Gershenfeld, H. K., Tsukamoto, A., Weissman, I. L. & Joho, R. Proc. natn. Acad. Sci. U.S.A. 78, 7674–7678 (1981).
Bothwell, A. L. M. et al. Cell 24, 625–637 (1981).
Sakano, H., Maki, R., Kurosawa, Y., Roeder, W. & Tonegawa, S. Nature 286, 676–683 (1980).
Kim, S., Davis, M., Sinn, E., Patten, P. & Hood, L. Cell 27, 573–581 (1981).
Kataoka, T., Nikaido, T., Miyata, T., Moriwaki, K. & Honjo, T. J. biol. Chem. 257, 277–285 (1982).
Crews, S., Griffen, J., Huang, H., Calame, K. & Hood, L. Cell 25, 59–66 (1981).
Bothwell, A. L. M., et al. Nature 290, 65–67 (1981).
Tonegawa, S., Maxam, A. M., Tizard, R., Bernard, O. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 75, 1485–1489 (1978).
Schreier, P. H., Bothwell, A. L. M., Mueller-Hill, B. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 78, 4495–4499 (1981).
Dugan, E. S., Bradshaw, R. A., Simms, E. S. & Eisen, H. N. Biochemistry 12, 5400–5416 (1973).
Azuma, T., Steiner, L. A. & Eisen, H. N. Proc. natn. Acad. Sci. U.S.A. 78, 569–573 (1981).
Blomberg, B. & Tonegawa, S. Proc. natn. Acad. Sci. U.S.A. 79, 530–533 (1982).
Miller, J., Selsing, E. & Storb, U. Nature 295, 428–430 (1982).
Hozumi, N. et al. Proc. natn. Acad. Sci. U.S.A. 78, 7019–7023 (1981).
Baltimore, D. Cell 26, 295–296 (1981).
Kocher, H. P., Berek, C., Schreier, M. H., Cosenza, H. & Jaton, J. C. Eur. J. Immun. 10, 264–267 (1980).
Gearhart, P. J., Johnson, N. D., Douglas, R. & Hood, L. Nature 291, 29–34 (1981).
Hieter, P. A., Hollis, G. F., Korsmeyer, S. J., Waldmann, T. A. & Leder, P. Nature 294, 536–540 (1981).
Maxam, A. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bothwell, A., Paskind, M., Reth, M. et al. Somatic variants of murine immunoglobulin λ light chains. Nature 298, 380–382 (1982). https://doi.org/10.1038/298380a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/298380a0
- Springer Nature Limited
This article is cited by
-
CD4+ T cells indirectly kill tumor cells via induction of cytotoxic macrophages in mouse models
Cancer Immunology, Immunotherapy (2019)
-
Biosynthetic antibody binding sites: Development of a single-chain Fv model based on antidinitrophenol IgA myeloma MOPC 315
Journal of Protein Chemistry (1991)
-
Synthesis and self-assembly of a functional monoclonal antibody in transgenic Nicotiana tabacum
Plant Molecular Biology (1990)
-
λ5, a new light-chain-related locus selectively expressed in pre-B lymphocytes
Nature (1986)
-
An unusual type of V–J joining diversifies the primary repertoire of mouse λ1 light chains
Nature (1985)