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. 1980 Apr;77(4):1937–1941. doi: 10.1073/pnas.77.4.1937

Transcription of mouse kappa chain genes: implications for allelic exclusion.

R P Perry, D E Kelley, C Coleclough, J G Seidman, P Leder, S Tonegawa, G Matthyssens, M Weigert
PMCID: PMC348624  PMID: 6769117

Abstract

The nuclear RNA from a large variety of kappa-producing plasmacytomas was size fractionated and analyzed with a series of cloned probes representing sequences encoding variable (V), joining (J), and constant (C) regions and selected intervening sequences. All of the plasmacytomas produce a nuclear RNA component that contains V kappa and C kappa sequences as well as the intervening sequence between J kappa and C kappa, and that has a distinctive size depending on which of the four J kappa segments is expressed (i.e., is present in the secreted kappa chain). These RNAs are the precursors of kappa mRNAs, which are transcribed from productively rearranged C kappa genes. Half of the plasmacytomas examined produce, in addition to a kappa mRNA precursor, a discrete component of about 8.4 kilobases that contains C kappa and upstream flanking sequences but lacks the expressed V region sequence. The ability to produce this component is always associated with the persistence in the tumor genome of an unrearranged (germline) J kappa-C kappa region. In tumors rearranged at both kappa loci the nonproductive allele is either transcriptionally silent or, in a minority of cases, transcribed and processed into a "fragment" mRNA lacking V region sequences. These results reveal that allelic exclusion can be effected at several levels of gene expression. They also provide some insight into the relative contributions of the V and C gene elements to this expression.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Gilmore-Herbert M., Hercules K., Komaromy M., Wall R. Variable and constant regions are separated in the 10-kbase transcription unit coding for immunoglobulin kappa light chains. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6044–6048. doi: 10.1073/pnas.75.12.6044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Hamlyn P. H., Browniee G. G., Cheng C. C., Gait M. J., Milstein C. Complete sequence of constant and 3' noncoding regions of an immunoglobulin mRNA using the dideoxynucleotide method of RNA sequencing. Cell. 1978 Nov;15(3):1067–1075. doi: 10.1016/0092-8674(78)90290-8. [DOI] [PubMed] [Google Scholar]
  3. Jeffreys A. J., Flavell R. A. The rabbit beta-globin gene contains a large large insert in the coding sequence. Cell. 1977 Dec;12(4):1097–1108. doi: 10.1016/0092-8674(77)90172-6. [DOI] [PubMed] [Google Scholar]
  4. Kuehl W. M., Kaplan B. A., Scharff M. D. Characterization of light chain and light chain constant region fragment mRNAs in MPC 11 mouse myeloma cells and variants. Cell. 1975 Jun;5(2):139–147. doi: 10.1016/0092-8674(75)90022-7. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Marcu K. B., Schibler U., Perry R. P. Nuclear transcripts of mouse heavy chain immunoglobulin genes contain only the expressed class of C-region sequences. Science. 1979 Jun 8;204(4397):1087–1088. doi: 10.1126/science.109919. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Perry R. P., Kelley D. E., Schibler U. Comparison of mRNA precursors in plasmacytomas producing closely related kappa chains. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3678–3682. doi: 10.1073/pnas.76.8.3678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Perry R. P., Kelley D. E., Schibler U., Huebner K., Croce C. M. Selective suppression of the transcription of ribosomal genes in mouse-human hybrid cells. J Cell Physiol. 1979 Mar;98(3):553–559. doi: 10.1002/jcp.1040980313. [DOI] [PubMed] [Google Scholar]
  10. Rabbitts T. H. Evidence for splicing of interrupted immunoglobulin variable and constant region sequences in nuclear RNA. Nature. 1978 Sep 28;275(5678):291–296. doi: 10.1038/275291a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Schechter I., Wolf O., Zemell R., Burstein Y. Structure and function of immunoglobulin genes and precursors. Fed Proc. 1979 Apr;38(5):1839–1845. [PubMed] [Google Scholar]
  14. Schibler U., Marcu K. B., Perry R. P. The synthesis and processing of the messenger RNAs specifying heavy and light chain immunoglobulins in MPC-11 cells. Cell. 1978 Dec;15(4):1495–1509. doi: 10.1016/0092-8674(78)90072-7. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  17. Steinmetz M., Zachau H. G., Mach B. Cloning of immunoglobulin kappa light chain genes from mouse liver and myeloma MOPC 173. Nucleic Acids Res. 1979 Jul 25;6(10):3213–3229. doi: 10.1093/nar/6.10.3213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tonegawa S., Hozumi N., Matthyssens G., Schuller R. Somatic changes in the content and context of immunoglobulin genes. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):877–889. doi: 10.1101/sqb.1977.041.01.097. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Wilson R., Miller J., Storb U. Rearrangement of immunoglobulin genes. Biochemistry. 1979 Oct 30;18(22):5013–5021. doi: 10.1021/bi00589a032. [DOI] [PubMed] [Google Scholar]

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