Abstract
Spontaneous deletions at the immunoglobulin heavy-chain locus are frequently found in myelomas, hybridomas and pre-B-cell lines. We have measured the rates for large and small deletions within the constant-region gene segment for mu chain in a pre-B-cell lines. The large deletions, which include the entire first and second exons, occurred at a rate of 1.7 X 10(-5) per cell generation. The small deletions, which span a few base pairs, occurred at a rate of 1.4 X 10(-7) per cell generation. The rate for the reversion of a termination codon in the second exon is even less than that for the small deletions and is 1000 times lower than the reversion rate that had been determined for the variable-region gene segment. Therefore, the variable-region gene segment is likely to be the preferred target for hypermutation.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adetugbo K., Milstein C., Secher D. S. Molecular analysis of spontaneous somatic mutants. Nature. 1977 Jan 27;265(5592):299–304. doi: 10.1038/265299a0. [DOI] [PubMed] [Google Scholar]
- Alt F. W., Rosenberg N., Casanova R. J., Thomas E., Baltimore D. Immunoglobulin heavy-chain expression and class switching in a murine leukaemia cell line. Nature. 1982 Mar 25;296(5855):325–331. doi: 10.1038/296325a0. [DOI] [PubMed] [Google Scholar]
- Baumal R., Birshtein B. K., Coffino P., Scharff M. D. Mutations in immunoglobulin-producing mouse myeloma cells. Science. 1973 Oct 12;182(4108):164–166. doi: 10.1126/science.182.4108.164. [DOI] [PubMed] [Google Scholar]
- Baumann B., Potash M. J., Köhler G. Consequences of frameshift mutations at the immunoglobulin heavy chain locus of the mouse. EMBO J. 1985 Feb;4(2):351–359. doi: 10.1002/j.1460-2075.1985.tb03636.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beck-Engeser G., Jäck H. M., Wabl M. Allelic inclusion in a pre-B-cell line that generates immunoglobulin heavy chain genes in vitro. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1060–1064. doi: 10.1073/pnas.84.4.1060. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Birshtein B. K., Preud'homme J. L., Scharff M. D. Variants of mouse myeloma cells that produce short immunoglobulin heavy chains. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3478–3482. doi: 10.1073/pnas.71.9.3478. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burrows P. D., Beck-Engeser G. B., Wabl M. R. Immunoglobulin heavy-chain class switching in a pre-B cell line is accompanied by DNA rearrangement. Nature. 1983 Nov 17;306(5940):243–246. doi: 10.1038/306243a0. [DOI] [PubMed] [Google Scholar]
- Burrows P. D., Beck G. B., Wabl M. R. Expression of mu and gamma immunoglobulin heavy chains in different cells of a cloned mouse lymphoid line. Proc Natl Acad Sci U S A. 1981 Jan;78(1):564–568. doi: 10.1073/pnas.78.1.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coffino P., Scharff M. D. Rate of somatic mutation in immunoglobulin production by mouse myeloma cells. Proc Natl Acad Sci U S A. 1971 Jan;68(1):219–223. doi: 10.1073/pnas.68.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldberg G. I., Vanin E. F., Zrolka A. M., Blattner F. R. Sequence of the gene for the constant region of the mu chain of Balb/c mouse immunoglobulin. Gene. 1981 Oct;15(1):33–42. doi: 10.1016/0378-1119(81)90102-5. [DOI] [PubMed] [Google Scholar]
- Kawakami T., Takahashi N., Honjo T. Complete nucleotide sequence of mouse immunoglobulin mu gene and comparison with other immunoglobulin heavy chain genes. Nucleic Acids Res. 1980 Sep 11;8(17):3933–3945. doi: 10.1093/nar/8.17.3933. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kenter A. L., Birshtein B. K. Genetic mechanism accounting for precise immunoglobulin domain deletion in a variant of MPC 11 myeloma cells. Science. 1979 Dec 14;206(4424):1307–1309. doi: 10.1126/science.117550. [DOI] [PubMed] [Google Scholar]
- Köhler G., Potash M. J., Lehrach H., Shulman M. J. Deletions in immunoglobulin mu chains. EMBO J. 1982;1(5):555–563. doi: 10.1002/j.1460-2075.1982.tb01208.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leptin M., Potash M. J., Grützmann R., Heusser C., Shulman M., Köhler G., Melchers F. Monoclonal antibodies specific for murine IgM I. Characterization of antigenic determinants on the four constant domains of the mu heavy chain. Eur J Immunol. 1984 Jun;14(6):534–542. doi: 10.1002/eji.1830140610. [DOI] [PubMed] [Google Scholar]
- Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
- Meyer J., Jäck H. M., Ellis N., Wabl M. High rate of somatic point mutation in vitro in and near the variable-region segment of an immunoglobulin heavy chain gene. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6950–6953. doi: 10.1073/pnas.83.18.6950. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morrison S. L. Murine heavy chain disease. Eur J Immunol. 1978 Mar;8(3):194–199. doi: 10.1002/eji.1830080311. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schuler W., Weiler I. J., Schuler A., Phillips R. A., Rosenberg N., Mak T. W., Kearney J. F., Perry R. P., Bosma M. J. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986 Sep 26;46(7):963–972. doi: 10.1016/0092-8674(86)90695-1. [DOI] [PubMed] [Google Scholar]
- Shulman M. J., Heusser C., Filkin C., Köhler G. Mutations affecting the structure and function of immunoglobulin M. Mol Cell Biol. 1982 Sep;2(9):1033–1043. doi: 10.1128/mcb.2.9.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
- Von Borstel R. C., Cain K. T., Steinberg C. M. Inheritance of spontaneous mutability in yeast. Genetics. 1971 Sep;69(1):17–27. doi: 10.1093/genetics/69.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wabl M. R., Beck-Engeser G. B., Burrows P. D. Allelic inclusion in the pre-B-cell line 18-81. Proc Natl Acad Sci U S A. 1984 Feb;81(3):867–870. doi: 10.1073/pnas.81.3.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wabl M. R., Burrows P. D. Expression of immunoglobulin heavy chain at a high level in the absence of a proposed immunoglobulin enhancer element in cis. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2452–2455. doi: 10.1073/pnas.81.8.2452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wabl M., Burrows P. D., von Gabain A., Steinberg C. Hypermutation at the immunoglobulin heavy chain locus in a pre-B-cell line. Proc Natl Acad Sci U S A. 1985 Jan;82(2):479–482. doi: 10.1073/pnas.82.2.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yelton D. E., Scharff M. D. Mutant monoclonal antibodies with alterations in biological functions. J Exp Med. 1982 Oct 1;156(4):1131–1148. doi: 10.1084/jem.156.4.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]