Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1984 Dec 1;3(12):3031–3035. doi: 10.1002/j.1460-2075.1984.tb02250.x

Unrearranged immunoglobulin lambda variable region is transcribed in kappa-producing myelomas.

D Picard, W Schaffner
PMCID: PMC557807  PMID: 6098463

Abstract

Most cell lines which secrete immunoglobulin kappa chains retain their lambda light chain genes in the germline configuration. We report that the lambda variable (V lambda) region is nevertheless transcribed in such kappa-secreting cells at a steady-state level of 1-10 RNA molecules per cell. These transcripts are developmentally regulated since they are not detectable in cell lines representative of earlier stages of B-lymphocyte differentiation. Therefore, the same cellular components which recognize and activate the unrearranged V lambda segment may also regulate the expression of the productive immunoglobulin genes. V lambda transcripts are initiated at the lambda gene cap site, include the variable region, and extend approximately 175 nucleotides into the adjacent spacer DNA. The transcripts are polyadenylated, properly spliced and transported into the cytoplasm. Interestingly, the spacer sequence contains an open reading frame which extends the V lambda coding region for an additional 37 amino acids. It is likely that V lambda transcripts are translated into an elongated protein which may play a regulatory role in B-lymphocyte differentiation.

Full text

PDF
3031

Images in this article

Selected References

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

  1. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  2. Bernard O., Hozumi N., Tonegawa S. Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell. 1978 Dec;15(4):1133–1144. doi: 10.1016/0092-8674(78)90041-7. [DOI] [PubMed] [Google Scholar]
  3. Blomberg B., Traunecker A., Eisen H., Tonegawa S. Organization of four mouse lambda light chain immunoglobulin genes. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3765–3769. doi: 10.1073/pnas.78.6.3765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brack C., Hirama M., Lenhard-Schuller R., Tonegawa S. A complete immunoglobulin gene is created by somatic recombination. Cell. 1978 Sep;15(1):1–14. doi: 10.1016/0092-8674(78)90078-8. [DOI] [PubMed] [Google Scholar]
  5. Brack C., Tonegawa S. Variable and constant parts of the immunoglobulin light chain gene of a mouse myeloma cell are 1250 nontranslated bases apart. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5652–5656. doi: 10.1073/pnas.74.12.5652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coleclough C., Perry R. P., Karjalainen K., Weigert M. Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression. Nature. 1981 Apr 2;290(5805):372–378. doi: 10.1038/290372a0. [DOI] [PubMed] [Google Scholar]
  7. Early P., Hood L. Allelic exclusion and nonproductive immunoglobulin gene rearrangements. Cell. 1981 Apr;24(1):1–3. doi: 10.1016/0092-8674(81)90492-x. [DOI] [PubMed] [Google Scholar]
  8. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  9. Gillies S. D., Morrison S. L., Oi V. T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. doi: 10.1016/0092-8674(83)90014-4. [DOI] [PubMed] [Google Scholar]
  10. Groudine M., Peretz M., Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. doi: 10.1128/mcb.1.3.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hieter P. A., Korsmeyer S. J., Waldmann T. A., Leder P. Human immunoglobulin kappa light-chain genes are deleted or rearranged in lambda-producing B cells. Nature. 1981 Apr 2;290(5805):368–372. doi: 10.1038/290368a0. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  14. Laskov R., Scharff M. D. Synthesis, assembly, and secretion of gamma globulin by mouse myeloma cells. I. Adaptation of the Merwin plasma cell tumor-11 to culture, cloning, and characterization of gamma globulin subunits. J Exp Med. 1970 Mar 1;131(3):515–541. doi: 10.1084/jem.131.3.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lundblad A., Steller R., Kabat E. A., Hirst J. W., Weigert M. G., Cohn M. Immunochemical studies on mouse myeloma proteins with specificity for dextran or for levan. Immunochemistry. 1972 May;9(5):535–544. doi: 10.1016/0019-2791(72)90063-8. [DOI] [PubMed] [Google Scholar]
  16. Mather E. L., Perry R. P. Transcriptional regulation of immunoglobulin V genes. Nucleic Acids Res. 1981 Dec 21;9(24):6855–6867. doi: 10.1093/nar/9.24.6855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Max E. E., Maizel J. V., Jr, Leder P. The nucleotide sequence of a 5.5-kilobase DNA segment containing the mouse kappa immunoglobulin J and C region genes. J Biol Chem. 1981 May 25;256(10):5116–5120. [PubMed] [Google Scholar]
  18. Nelson K. J., Haimovich J., Perry R. P. Characterization of productive and sterile transcripts from the immunoglobulin heavy-chain locus: processing of micron and muS mRNA. Mol Cell Biol. 1983 Jul;3(7):1317–1332. doi: 10.1128/mcb.3.7.1317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Neuberger M. S. Expression and regulation of immunoglobulin heavy chain gene transfected into lymphoid cells. EMBO J. 1983;2(8):1373–1378. doi: 10.1002/j.1460-2075.1983.tb01594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ono M., Kawakami M. Existence of both kappa and lambda light chain messenger RNA sequences in mouse myeloma, MOPC-104E, known as a lambda chain producer. Biochem Biophys Res Commun. 1977 Jan 24;74(2):796–802. doi: 10.1016/0006-291x(77)90373-4. [DOI] [PubMed] [Google Scholar]
  21. Paige C. J., Kincade P. W., Ralph P. Murine B cell leukemia line with inducible surface immunoglobulin expression. J Immunol. 1978 Aug;121(2):641–647. [PubMed] [Google Scholar]
  22. Perry R. P., Coleclough C., Weigert M. Reorganization and expression of immunoglobulin genes: status of allelic elements. Cold Spring Harb Symp Quant Biol. 1981;45(Pt 2):925–933. doi: 10.1101/sqb.1981.045.01.109. [DOI] [PubMed] [Google Scholar]
  23. Perry R. P., Kelley D. E., Coleclough C., Seidman J. G., Leder P., Tonegawa S., Matthyssens G., Weigert M. Transcription of mouse kappa chain genes: implications for allelic exclusion. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1937–1941. doi: 10.1073/pnas.77.4.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Picard D., Schaffner W. A lymphocyte-specific enhancer in the mouse immunoglobulin kappa gene. Nature. 1984 Jan 5;307(5946):80–82. doi: 10.1038/307080a0. [DOI] [PubMed] [Google Scholar]
  25. Picard D., Schaffner W. Correct transcription of a cloned mouse immunoglobulin gene in vivo. Proc Natl Acad Sci U S A. 1983 Jan;80(2):417–421. doi: 10.1073/pnas.80.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Queen C., Stafford J. Fine mapping of an immunoglobulin gene activator. Mol Cell Biol. 1984 Jun;4(6):1042–1049. doi: 10.1128/mcb.4.6.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rusconi S., Schaffner W. Transformation of frog embryos with a rabbit beta-globin gene. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5051–5055. doi: 10.1073/pnas.78.8.5051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schibler U., Hagenbüchle O., Wellauer P. K., Pittet A. C. Two promoters of different strengths control the transcription of the mouse alpha-amylase gene Amy-1a in the parotid gland and the liver. Cell. 1983 Jun;33(2):501–508. doi: 10.1016/0092-8674(83)90431-2. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Selsing E., Miller J., Wilson R., Storb U. Evolution of mouse immunoglobulin lambda genes. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4681–4685. doi: 10.1073/pnas.79.15.4681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Storb U., Arp B. Methylation patterns of immunoglobulin genes in lymphoid cells: correlation of expression and differentiation with undermethylation. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6642–6646. doi: 10.1073/pnas.80.21.6642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Van Ness B. G., Weigert M., Coleclough C., Mather E. L., Kelley D. E., Perry R. P. Transcription of the unrearranged mouse C kappa locus: sequence of the initiation region and comparison of activity with a rearranged V kappa-C kappa gene. Cell. 1981 Dec;27(3 Pt 2):593–602. doi: 10.1016/0092-8674(81)90401-3. [DOI] [PubMed] [Google Scholar]
  33. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  34. Warner N. L., Daley M. J., Richey J., Spellman C. Flow cytometry analysis of murine B cell lymphoma differentiation. Immunol Rev. 1979;48:197–243. doi: 10.1111/j.1600-065x.1979.tb00304.x. [DOI] [PubMed] [Google Scholar]
  35. Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES