Abstract
A site-specific recombination event is responsible for the somatic activation of immunoglobulin genes and for generating a major share of immunoglobulin gene diversity. Although several possible mechanisms can be proposed to account for this process, recombinatio accompanied by deletion is a particularly attractive mechanism because it might utilize inverted repeat sequences noted on the 3' side of all variable regions and on the 5' side of all joining site segments thus far studied. Testing this model is complicated by the fact that antibody cells are at least diploid and gene segments on the inactive chromosome can obscure deletions occurring within the active gene. Accordingly, we have screened several immunoglobulin-producing plasmacytoma lines to select those in which both chromosomes are rearranged. By using appropriate cell lines and variable and joining region probes in in situ hybridization experiments, we show that recombination is accompanied by the deletion of both variable and joining region genes. These experiments also allow us to map the site of V/J recombination of several active immunoglobulin genes and suggest an order and orientation for variable, joining, and constant region sequences.
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.
- Burstein Y., Schechter I. Amino acid sequence of the NH2-terminal extra piece segments of the precursors of mouse immunoglobulin lambda1-type and kappa-type light chains. Proc Natl Acad Sci U S A. 1977 Feb;74(2):716–720. doi: 10.1073/pnas.74.2.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohn M., Notani G., Rice S. A. Characterization of the antibody to the C-carbohydrate produced by a transplantable mouse plasmacytoma. Immunochemistry. 1969 Jan;6(1):111–123. doi: 10.1016/0019-2791(69)90183-9. [DOI] [PubMed] [Google Scholar]
- Dreyer W. J., Bennett J. C. The molecular basis of antibody formation: a paradox. Proc Natl Acad Sci U S A. 1965 Sep;54(3):864–869. doi: 10.1073/pnas.54.3.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gally J. A., Edelman G. M. Somatic translocation of antibody genes. Nature. 1970 Jul 25;227(5256):341–348. doi: 10.1038/227341a0. [DOI] [PubMed] [Google Scholar]
- Hicks J. B., Herskowitz I. Interconversion of Yeast Mating Types I. Direct Observations of the Action of the Homothallism (HO) Gene. Genetics. 1976 Jun;83(2):245–258. doi: 10.1093/genetics/83.2.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hozumi N., Tonegawa S. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3628–3632. doi: 10.1073/pnas.73.10.3628. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kabat D. Gene selection in hemoglobin and in antibody-synthesizing cells. Science. 1972 Jan 14;175(4018):134–140. doi: 10.1126/science.175.4018.134. [DOI] [PubMed] [Google Scholar]
- Kleckner N., Ross D. G. Translocation and other recombination events involving the tetracycline-resistance element Tn10. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 2):1233–1246. doi: 10.1101/sqb.1979.043.01.140. [DOI] [PubMed] [Google Scholar]
- Kuehl W. M., Scharff M. D. Synthesis of a carboxyl-terminal (constant region) fragment of the immunoglobulin light chain by a mouse myeloma cell line. J Mol Biol. 1974 Nov 5;89(3):409–421. doi: 10.1016/0022-2836(74)90472-0. [DOI] [PubMed] [Google Scholar]
- Lenhard-Schuller R., Hohn B., Brack C., Hirama M., Tonegawa S. DNA clones containing mouse immunoglobulin kappa chain genes isolated by in vitro packaging into phage lambda coats. Proc Natl Acad Sci U S A. 1978 Oct;75(10):4709–4713. doi: 10.1073/pnas.75.10.4709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Max E. E., Seidman J. G., Leder P. Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3450–3454. doi: 10.1073/pnas.76.7.3450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Max E. E., Seidman J. G., Miller H., Leder P. Variation in the crossover point of kappa immunoglobulin gene V-J recombination: evidence from a cryptic gene. Cell. 1980 Oct;21(3):793–799. doi: 10.1016/0092-8674(80)90442-0. [DOI] [PubMed] [Google Scholar]
- Rose S. M., Kuehl W. M., Smith G. P. Cloned MPC 11 myeloma cells express two kappa genes: a gene for a complete light chain and a gene for a constant region polypeptide. Cell. 1977 Oct;12(2):453–462. doi: 10.1016/0092-8674(77)90121-0. [DOI] [PubMed] [Google Scholar]
- Sakano H., Hüppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979 Jul 26;280(5720):288–294. doi: 10.1038/280288a0. [DOI] [PubMed] [Google Scholar]
- Seidman J. G., Leder A., Edgell M. H., Polsky F., Tilghman S. M., Tiemeier D. C., Leder P. Multiple related immunoglobulin variable-region genes identified by cloning and sequence analysis. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3881–3885. doi: 10.1073/pnas.75.8.3881. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seidman J. G., Leder A., Nau M., Norman B., Leder P. Antibody diversity. Science. 1978 Oct 6;202(4363):11–17. doi: 10.1126/science.99815. [DOI] [PubMed] [Google Scholar]
- Seidman J. G., Leder P. A mutant immunoglobulin light chain is formed by aberrant DNA- and RNA-splicing events. Nature. 1980 Aug 21;286(5775):779–783. doi: 10.1038/286779a0. [DOI] [PubMed] [Google Scholar]
- Seidman J. G., Leder P. The arrangement and rearrangement of antibody genes. Nature. 1978 Dec 21;276(5690):790–795. doi: 10.1038/276790a0. [DOI] [PubMed] [Google Scholar]
- Seidman J. G., Max E. E., Leder P. A kappa-immunoglobulin gene is formed by site-specific recombination without further somatic mutation. Nature. 1979 Aug 2;280(5721):370–375. doi: 10.1038/280370a0. [DOI] [PubMed] [Google Scholar]
- Silverman M., Simon M. Phase variation: genetic analysis of switching mutants. Cell. 1980 Apr;19(4):845–854. doi: 10.1016/0092-8674(80)90075-6. [DOI] [PubMed] [Google Scholar]
- Smith G. P. Sequence of the full-length immunoglobulin kappa-chain of mouse myeloma MPC 11. Biochem J. 1978 May 1;171(2):337–347. doi: 10.1042/bj1710337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Svasti J., Milstein C. The complete amino acid sequence of a mouse kappa light chain. Biochem J. 1972 Jun;128(2):427–444. doi: 10.1042/bj1280427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tilghman S. M., Tiemeier D. C., Polsky F., Edgell M. H., Seidman J. G., Leder A., Enquist L. W., Norman B., Leder P. Cloning specific segments of the mammalian genome: bacteriophage lambda containing mouse globin and surrounding gene sequences. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4406–4410. doi: 10.1073/pnas.74.10.4406. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valbuena O., Marcu K. B., Weigert M., Perry R. P. Multiplicity of germline genes specifying a group of related mouse kappa chains with implications for the generation of immunoglobulin diversity. Nature. 1978 Dec 21;276(5690):780–784. doi: 10.1038/276780a0. [DOI] [PubMed] [Google Scholar]