Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1988 May;8(5):1932–1939. doi: 10.1128/mcb.8.5.1932

Genes activated in the presence of an immunoglobulin enhancer or promoter are negatively regulated by a T-lymphoma cell line.

D M Zaller 1, H Yu 1, L A Eckhardt 1
PMCID: PMC363371  PMID: 3133550

Abstract

The tissue-specific expression of immunoglobulin genes can be partially explained by a requirement for activating factors found only in B lymphocytes and their derivatives. However, loss of immunoglobulin expression upon fusion of an immunoglobulin-producing myeloma cell with a T lymphoma cell (BW5147) or fibroblast (L cell) suggests that negatively acting factors also play a role in the tissue specificity of immunoglobulin genes. Expression of a cloned immunoglobulin heavy-chain gene introduced into myeloma cells was suppressed after fusion of the myeloma transformants with BW5147. The presence of either the immunoglobulin heavy-chain enhancer or promoter conferred suppression, under similar conditions, upon a heterologous gene that is normally expressed in both B and T lymphocytes. These immunoglobulin heavy-chain gene control regions, or gene modifications induced by them, are subject to negative control by T-lymphocyte-derived factors.

Full text

PDF
1934

Images in this article

1934Image
on p.1934
1934Image
on p.1934
1935Image
on p.1935
1936Image
on p.1936
1936Image
on p.1936

Selected References

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

  1. Aguilera R. J., Hope T. J., Sakano H. Characterization of immunoglobulin enhancer deletions in murine plasmacytomas. EMBO J. 1985 Dec 30;4(13B):3689–3693. doi: 10.1002/j.1460-2075.1985.tb04136.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alt F. W., Blackwell T. K., DePinho R. A., Reth M. G., Yancopoulos G. D. Regulation of genome rearrangement events during lymphocyte differentiation. Immunol Rev. 1986 Feb;89:5–30. doi: 10.1111/j.1600-065x.1986.tb01470.x. [DOI] [PubMed] [Google Scholar]
  3. Alt F. W., Rosenberg N., Enea V., Siden E., Baltimore D. Multiple immunoglobulin heavy-chain gene transcripts in Abelson murine leukemia virus-transformed lymphoid cell lines. Mol Cell Biol. 1982 Apr;2(4):386–400. doi: 10.1128/mcb.2.4.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Atchison M. L., Perry R. P. The role of the kappa enhancer and its binding factor NF-kappa B in the developmental regulation of kappa gene transcription. Cell. 1987 Jan 16;48(1):121–128. doi: 10.1016/0092-8674(87)90362-x. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Blackman M. A., Koshland M. E. Specific 5' and 3' regions of the mu-chain gene are undermethylated at distinct stages of B-cell differentiation. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3809–3813. doi: 10.1073/pnas.82.11.3809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bohmann D., Keller W., Dale T., Schöler H. R., Tebb G., Mattaj I. W. A transcription factor which binds to the enhancers of SV40, immunoglobulin heavy chain and U2 snRNA genes. Nature. 1987 Jan 15;325(6101):268–272. doi: 10.1038/325268a0. [DOI] [PubMed] [Google Scholar]
  8. Clayton D. F., Darnell J. E., Jr Changes in liver-specific compared to common gene transcription during primary culture of mouse hepatocytes. Mol Cell Biol. 1983 Sep;3(9):1552–1561. doi: 10.1128/mcb.3.9.1552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coffino P., Knowles B., Nathenson S. G., Scharff M. D. Suppression of immunoglobulin synthesis by cellular hybridization. Nat New Biol. 1971 May 19;231(20):87–90. doi: 10.1038/newbio231087a0. [DOI] [PubMed] [Google Scholar]
  10. Eckhardt L. A., Birshtein B. K. Independent immunoglobulin class-switch events occurring in a single myeloma cell line. Mol Cell Biol. 1985 Apr;5(4):856–868. doi: 10.1128/mcb.5.4.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ephrussi A., Church G. M., Tonegawa S., Gilbert W. B lineage--specific interactions of an immunoglobulin enhancer with cellular factors in vivo. Science. 1985 Jan 11;227(4683):134–140. doi: 10.1126/science.3917574. [DOI] [PubMed] [Google Scholar]
  12. Falkner F. G., Zachau H. G. Correct transcription of an immunoglobulin kappa gene requires an upstream fragment containing conserved sequence elements. Nature. 1984 Jul 5;310(5972):71–74. doi: 10.1038/310071a0. [DOI] [PubMed] [Google Scholar]
  13. Foster J., Stafford J., Queen C. An immunoglobulin promoter displays cell-type specificity independently of the enhancer. 1985 May 30-Jun 5Nature. 315(6018):423–425. doi: 10.1038/315423a0. [DOI] [PubMed] [Google Scholar]
  14. Fromm M., Berg P. Deletion mapping of DNA regions required for SV40 early region promoter function in vivo. J Mol Appl Genet. 1982;1(5):457–481. [PubMed] [Google Scholar]
  15. Gerster T., Matthias P., Thali M., Jiricny J., Schaffner W. Cell type-specificity elements of the immunoglobulin heavy chain gene enhancer. EMBO J. 1987 May;6(5):1323–1330. doi: 10.1002/j.1460-2075.1987.tb02371.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Gopal T. V., Shimada T., Baur A. W., Nienhuis A. W. Contribution of promoter to tissue-specific expression of the mouse immunoglobulin kappa gene. Science. 1985 Sep 13;229(4718):1102–1104. doi: 10.1126/science.2994213. [DOI] [PubMed] [Google Scholar]
  18. Greenberg A., Ber R., Kra-Oz Z., Laskov R. Extinction of expression of immunoglobulin genes in myeloma X fibroblast somatic cell hybrids. Mol Cell Biol. 1987 Feb;7(2):936–939. doi: 10.1128/mcb.7.2.936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
  20. Hen R., Borrelli E., Chambon P. Repression of the immunoglobulin heavy chain enhancer by the adenovirus-2 E1A products. Science. 1985 Dec 20;230(4732):1391–1394. doi: 10.1126/science.2999984. [DOI] [PubMed] [Google Scholar]
  21. Hyman R., Stallings V. Complementation patterns of Thy-1 variants and evidence that antigen loss variants "pre-exist" in the parental population. J Natl Cancer Inst. 1974 Feb;52(2):429–436. doi: 10.1093/jnci/52.2.429. [DOI] [PubMed] [Google Scholar]
  22. Imler J. L., Lemaire C., Wasylyk C., Wasylyk B. Negative regulation contributes to tissue specificity of the immunoglobulin heavy-chain enhancer. Mol Cell Biol. 1987 Jul;7(7):2558–2567. doi: 10.1128/mcb.7.7.2558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ishihara T., Kudo A., Watanabe T. Induction of immunoglobulin gene expression in mouse fibroblasts by cycloheximide treatment. J Exp Med. 1984 Dec 1;160(6):1937–1942. doi: 10.1084/jem.160.6.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Iverson G. M., Goldsby R. A., Herzenberg L. A. Expression of Thy 1.2 antigen on hybrids of B cells and a T lymphoma. Curr Top Microbiol Immunol. 1978;81:192–194. doi: 10.1007/978-3-642-67448-8_31. [DOI] [PubMed] [Google Scholar]
  25. Kadesch T., Zervos P., Ruezinsky D. Functional analysis of the murine IgH enhancer: evidence for negative control of cell-type specificity. Nucleic Acids Res. 1986 Oct 24;14(20):8209–8221. doi: 10.1093/nar/14.20.8209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kemp D. J., Harris A. W., Cory S., Adams J. M. Expression of the immunoglobulin C mu gene in mouse T and B lymphoid and myeloid cell lines. Proc Natl Acad Sci U S A. 1980 May;77(5):2876–2880. doi: 10.1073/pnas.77.5.2876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Killary A. M., Fournier R. E. A genetic analysis of extinction: trans-dominant loci regulate expression of liver-specific traits in hepatoma hybrid cells. Cell. 1984 Sep;38(2):523–534. doi: 10.1016/0092-8674(84)90507-5. [DOI] [PubMed] [Google Scholar]
  28. Klein S., Gerster T., Picard D., Radbruch A., Schaffner W. Evidence for transient requirement of the IgH enhancer. Nucleic Acids Res. 1985 Dec 20;13(24):8901–8912. doi: 10.1093/nar/13.24.8901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Klein S., Sablitzky F., Radbruch A. Deletion of the IgH enhancer does not reduce immunoglobulin heavy chain production of a hybridoma IgD class switch variant. EMBO J. 1984 Nov;3(11):2473–2476. doi: 10.1002/j.1460-2075.1984.tb02158.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Landolfi N. F., Capra J. D., Tucker P. W. Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences. Nature. 1986 Oct 9;323(6088):548–551. doi: 10.1038/323548a0. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Maeda H., Kitamura D., Kudo A., Araki K., Watanabe T. Trans-acting nuclear protein responsible for induction of rearranged human immunoglobulin heavy chain gene. Cell. 1986 Apr 11;45(1):25–33. doi: 10.1016/0092-8674(86)90534-9. [DOI] [PubMed] [Google Scholar]
  33. Mason J. O., Williams G. T., Neuberger M. S. Transcription cell type specificity is conferred by an immunoglobulin VH gene promoter that includes a functional consensus sequence. Cell. 1985 Jun;41(2):479–487. doi: 10.1016/s0092-8674(85)80021-0. [DOI] [PubMed] [Google Scholar]
  34. Mercola M., Goverman J., Mirell C., Calame K. Immunoglobulin heavy-chain enhancer requires one or more tissue-specific factors. Science. 1985 Jan 18;227(4684):266–270. doi: 10.1126/science.3917575. [DOI] [PubMed] [Google Scholar]
  35. Mizushima-Sugano J., Roeder R. G. Cell-type-specific transcription of an immunoglobulin kappa light chain gene in vitro. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8511–8515. doi: 10.1073/pnas.83.22.8511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Mulligan R. C., Berg P. Expression of a bacterial gene in mammalian cells. Science. 1980 Sep 19;209(4463):1422–1427. doi: 10.1126/science.6251549. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Oi V. T., Morrison S. L., Herzenberg L. A., Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. doi: 10.1073/pnas.80.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Periman P. IgG synthesis in hybrid cells from an antibody-producing mouse myeloma and an L cell substrain. Nature. 1970 Dec 12;228(5276):1086–1087. doi: 10.1038/2281086a0. [DOI] [PubMed] [Google Scholar]
  40. Picard D., Schaffner W. Cell-type preference of immunoglobulin kappa and lambda gene promoters. EMBO J. 1985 Nov;4(11):2831–2838. doi: 10.1002/j.1460-2075.1985.tb04011.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schöler H. R., Gruss P. Cell type-specific transcriptional enhancement in vitro requires the presence of trans-acting factors. EMBO J. 1985 Nov;4(11):3005–3013. doi: 10.1002/j.1460-2075.1985.tb04036.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
  43. Sive H. L., Roeder R. G. Interaction of a common factor with conserved promoter and enhancer sequences in histone H2B, immunoglobulin, and U2 small nuclear RNA (snRNA) genes. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6382–6386. doi: 10.1073/pnas.83.17.6382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Staudt L. M., Singh H., Sen R., Wirth T., Sharp P. A., Baltimore D. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature. 1986 Oct 16;323(6089):640–643. doi: 10.1038/323640a0. [DOI] [PubMed] [Google Scholar]
  45. Stavnezer-Nordgren J., Sirlin S. Specificity of immunoglobulin heavy chain switch correlates with activity of germline heavy chain genes prior to switching. EMBO J. 1986 Jan;5(1):95–102. doi: 10.1002/j.1460-2075.1986.tb04182.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. 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]
  47. Wang X. F., Calame K. SV40 enhancer-binding factors are required at the establishment but not the maintenance step of enhancer-dependent transcriptional activation. Cell. 1986 Oct 24;47(2):241–247. doi: 10.1016/0092-8674(86)90446-0. [DOI] [PubMed] [Google Scholar]
  48. Wasylyk C., Wasylyk B. The immunoglobulin heavy-chain B-lymphocyte enhancer efficiently stimulates transcription in non-lymphoid cells. EMBO J. 1986 Mar;5(3):553–560. doi: 10.1002/j.1460-2075.1986.tb04246.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Weinberger J., Baltimore D., Sharp P. A. Distinct factors bind to apparently homologous sequences in the immunoglobulin heavy-chain enhancer. 1986 Aug 28-Sep 3Nature. 322(6082):846–848. doi: 10.1038/322846a0. [DOI] [PubMed] [Google Scholar]
  50. Yu H., Eckhardt L. A. DNA rearrangement causes a high rate of spontaneous mutation at the immunoglobulin heavy-chain locus of a mouse myeloma cell line. Mol Cell Biol. 1986 Dec;6(12):4228–4235. doi: 10.1128/mcb.6.12.4228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Zaller D. M., Eckhardt L. A. Deletion of a B-cell-specific enhancer affects transfected, but not endogenous, immunoglobulin heavy-chain gene expression. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5088–5092. doi: 10.1073/pnas.82.15.5088. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES