Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1989 Jun 1;169(6):2059–2071. doi: 10.1084/jem.169.6.2059

Interleukin 3 (IL-3) induces transcription from nonrearranged T cell receptor gamma loci in IL-3-dependent cell lines

PMCID: PMC2189342  PMID: 2543731

Abstract

The expression of the murine TCR-gamma genes was examined in a series of IL-3-dependent and growth factor-independent cell lines. All of the IL-3-dependent cell lines, but none of the IL-3-independent lines, expressed high levels of one or more of the gamma genes but did not express the TCR-beta genes. None of the cell lines expressing the gamma loci contained detectable genomic gamma gene rearrangements. Sequencing of cDNA clones from two of the cell lines demonstrated that transcription was from nonrearranged gamma loci based on the presence of sequences in the cDNAs that are found immediately 5' of the J gamma 4 and J gamma 2 genes. The expression of gamma transcripts was dependent upon IL-3 and no transcripts were detectable within 6-8 h after the removal of IL-3. Readdition of IL-3, but not granulocyte CSF, resulted in the reappearance of gamma transcripts within 30 min. The results demonstrate that IL-3 regulates the expression of nonrearranged gamma loci. Since expression is required for rearrangement, it can be hypothesized that IL-3 may influence the ability of lymphoid/myeloid progenitors to commit to the T cell lineage.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. 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]
  2. Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
  3. Blackwell T. K., Moore M. W., Yancopoulos G. D., Suh H., Lutzker S., Selsing E., Alt F. W. Recombination between immunoglobulin variable region gene segments is enhanced by transcription. Nature. 1986 Dec 11;324(6097):585–589. doi: 10.1038/324585a0. [DOI] [PubMed] [Google Scholar]
  4. Chien Y. H., Iwashima M., Kaplan K. B., Elliott J. F., Davis M. M. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. 1987 Jun 25-Jul 1Nature. 327(6124):677–682. doi: 10.1038/327677a0. [DOI] [PubMed] [Google Scholar]
  5. Cook W. D., Balaton A. M. T-cell receptor and immunoglobulin genes are rearranged together in Abelson virus-transformed pre-B and pre-T cells. Mol Cell Biol. 1987 Jan;7(1):266–272. doi: 10.1128/mcb.7.1.266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dean M., Cleveland J. L., Rapp U. R., Ihle J. N. Role of myc in the abrogation of IL3 dependence of myeloid FDC-P1 cells. Oncogene Res. 1987 Aug;1(3):279–296. [PubMed] [Google Scholar]
  7. Dexter T. M., Garland J., Scott D., Scolnick E., Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. doi: 10.1084/jem.152.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Greenberger J. S., Davisson P. B., Gans P. J., Moloney W. C. In vitro induction of continuous acute promyelocytic leukemia cell lines by Friend or Abelson murine leukemia virus. Blood. 1979 May;53(5):987–1001. [PubMed] [Google Scholar]
  9. Greenberger J. S., Sakakeeny M. A., Humphries R. K., Eaves C. J., Eckner R. J. Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines. Proc Natl Acad Sci U S A. 1983 May;80(10):2931–2935. doi: 10.1073/pnas.80.10.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haars R., Kronenberg M., Gallatin W. M., Weissman I. L., Owen F. L., Hood L. Rearrangement and expression of T cell antigen receptor and gamma genes during thymic development. J Exp Med. 1986 Jul 1;164(1):1–24. doi: 10.1084/jem.164.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hayday A. C., Saito H., Gillies S. D., Kranz D. M., Tanigawa G., Eisen H. N., Tonegawa S. Structure, organization, and somatic rearrangement of T cell gamma genes. Cell. 1985 Feb;40(2):259–269. doi: 10.1016/0092-8674(85)90140-0. [DOI] [PubMed] [Google Scholar]
  12. Heilig J. S., Tonegawa S. Diversity of murine gamma genes and expression in fetal and adult T lymphocytes. 1986 Aug 28-Sep 3Nature. 322(6082):836–840. doi: 10.1038/322836a0. [DOI] [PubMed] [Google Scholar]
  13. Holmes K. L., Palaszynski E., Fredrickson T. N., Morse H. C., 3rd, Ihle J. N. Correlation of cell-surface phenotype with the establishment of interleukin 3-dependent cell lines from wild-mouse murine leukemia virus-induced neoplasms. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6687–6691. doi: 10.1073/pnas.82.19.6687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ihle J. N., Keller J., Henderson L., Klein F., Palaszynski E. Procedures for the purification of interleukin 3 to homogeneity. J Immunol. 1982 Dec;129(6):2431–2436. [PubMed] [Google Scholar]
  15. Ihle J. N., Keller J., Oroszlan S., Henderson L. E., Copeland T. D., Fitch F., Prystowsky M. B., Goldwasser E., Schrader J. W., Palaszynski E. Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity. J Immunol. 1983 Jul;131(1):282–287. [PubMed] [Google Scholar]
  16. Ihle J. N., Weinstein Y. Immunological regulation of hematopoietic/lymphoid stem cell differentiation by interleukin 3. Adv Immunol. 1986;39:1–50. doi: 10.1016/s0065-2776(08)60347-8. [DOI] [PubMed] [Google Scholar]
  17. Iwamoto A., Rupp F., Ohashi P. S., Walker C. L., Pircher H., Joho R., Hengartner H., Mak T. W. T cell-specific gamma genes in C57BL/10 mice. Sequence and expression of new constant and variable region genes. J Exp Med. 1986 May 1;163(5):1203–1212. doi: 10.1084/jem.163.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Joyner A., Keller G., Phillips R. A., Bernstein A. Retrovirus transfer of a bacterial gene into mouse haematopoietic progenitor cells. Nature. 1983 Oct 6;305(5934):556–558. doi: 10.1038/305556a0. [DOI] [PubMed] [Google Scholar]
  19. Keller G., Paige C., Gilboa E., Wagner E. F. Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors. Nature. 1985 Nov 14;318(6042):149–154. doi: 10.1038/318149a0. [DOI] [PubMed] [Google Scholar]
  20. Kronenberg M., Siu G., Hood L. E., Shastri N. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu Rev Immunol. 1986;4:529–591. doi: 10.1146/annurev.iy.04.040186.002525. [DOI] [PubMed] [Google Scholar]
  21. Lew A. M., Pardoll D. M., Maloy W. L., Fowlkes B. J., Kruisbeek A., Cheng S. F., Germain R. N., Bluestone J. A., Schwartz R. H., Coligan J. E. Characterization of T cell receptor gamma chain expression in a subset of murine thymocytes. Science. 1986 Dec 12;234(4782):1401–1405. doi: 10.1126/science.3787252. [DOI] [PubMed] [Google Scholar]
  22. Lutzker S., Alt F. W. Structure and expression of germ line immunoglobulin gamma 2b transcripts. Mol Cell Biol. 1988 Apr;8(4):1849–1852. doi: 10.1128/mcb.8.4.1849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lutzker S., Rothman P., Pollock R., Coffman R., Alt F. W. Mitogen- and IL-4-regulated expression of germ-line Ig gamma 2b transcripts: evidence for directed heavy chain class switching. Cell. 1988 Apr 22;53(2):177–184. doi: 10.1016/0092-8674(88)90379-0. [DOI] [PubMed] [Google Scholar]
  24. Morishita K., Kubota N., Asano S., Kaziro Y., Nagata S. Molecular cloning and characterization of cDNA for human myeloperoxidase. J Biol Chem. 1987 Mar 15;262(8):3844–3851. [PubMed] [Google Scholar]
  25. Palacios R., Kiefer M., Brockhaus M., Karjalainen K., Dembić Z., Kisielow P., von Boehmer H. Molecular, cellular, and functional properties of bone marrow T lymphocyte progenitor clones. J Exp Med. 1987 Jul 1;166(1):12–32. doi: 10.1084/jem.166.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Palacios R., Steinmetz M. Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell. 1985 Jul;41(3):727–734. doi: 10.1016/s0092-8674(85)80053-2. [DOI] [PubMed] [Google Scholar]
  27. Raulet D. H., Garman R. D., Saito H., Tonegawa S. Developmental regulation of T-cell receptor gene expression. Nature. 1985 Mar 7;314(6006):103–107. doi: 10.1038/314103a0. [DOI] [PubMed] [Google Scholar]
  28. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Suda T., Suda J., Ogawa M., Ihle J. N. Permissive role of interleukin 3 (IL-3) in proliferation and differentiation of multipotential hemopoietic progenitors in culture. J Cell Physiol. 1985 Aug;124(2):182–190. doi: 10.1002/jcp.1041240203. [DOI] [PubMed] [Google Scholar]
  31. Warren H. S., Hargreaves J., Hapel A. J. Some interleukin-3 dependent mast-cell lines also respond to interleukin-2. Lymphokine Res. 1985 Summer;4(3):195–204. [PubMed] [Google Scholar]
  32. Weinstein Y., Lindner H. R., Eckstein B. Thymus metabolises progesterone- possible enzymatic marker for T lymphocytes. Nature. 1977 Apr 14;266(5603):632–633. doi: 10.1038/266632a0. [DOI] [PubMed] [Google Scholar]
  33. Williams D. A., Lemischka I. R., Nathan D. G., Mulligan R. C. Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse. Nature. 1984 Aug 9;310(5977):476–480. doi: 10.1038/310476a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES