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. 1987 Jul 1;166(1):12–32. doi: 10.1084/jem.166.1.12

Molecular, cellular, and functional properties of bone marrow T lymphocyte progenitor clones [published erratum appears in J Exp Med 1988 Jun 1;167(6):2023]

PMCID: PMC2188637  PMID: 3496413

Abstract

The continuous proliferating bone marrow clones C4-77, C4-86, and C4-95 express low levels of Thy-1 and Ly-1 surface antigens, but no detectable surface antigens normally present on thymocytes, peripheral mature T lymphocytes, cells of the B lymphocyte or myeloid lineages. They contain the T cell antigen receptor genes alpha, beta, and the T cell-specific gene gamma in the germline configuration, and they express functional receptors for IL-3 and nonfunctional receptors for IL-2. The C4 clones are able to home and undergo differentiation in the thymus of sublethally irradiated mice and give rise in vivo to phenotypically and functionally mature peripheral T lymphocytes displaying several antigen specificities. In vitro 5-Azacytidine induces the C4 clones to express Lyt-2 and L3T4 T cell differentiation antigens, and renders them amenable to be switched from IL-3 to IL-2 dependence. However, the C4 clones seem incapable of giving rise to B lymphocytes either in vivo or in vitro. They self-renew in vitro in the presence of IL-3 every 12-14 h. We conclude that the C4 clones represent cells at the earliest stage of T cell development, i.e., Pro- T lymphocytes.

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Selected References

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  1. Abramson S., Miller R. G., Phillips R. A. The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems. J Exp Med. 1977 Jun 1;145(6):1567–1579. doi: 10.1084/jem.145.6.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  3. Davis M. M. Molecular genetics of the T cell-receptor beta chain. Annu Rev Immunol. 1985;3:537–560. doi: 10.1146/annurev.iy.03.040185.002541. [DOI] [PubMed] [Google Scholar]
  4. Dembić Z., Haas W., Weiss S., McCubrey J., Kiefer H., von Boehmer H., Steinmetz M. Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature. 1986 Mar 20;320(6059):232–238. doi: 10.1038/320232a0. [DOI] [PubMed] [Google Scholar]
  5. Devos R., Plaetinck G., Cheroutre H., Simons G., Degrave W., Tavernier J., Remaut E., Fiers W. Molecular cloning of human interleukin 2 cDNA and its expression in E. coli. Nucleic Acids Res. 1983 Jul 11;11(13):4307–4323. doi: 10.1093/nar/11.13.4307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dick J. E., Magli M. C., Huszar D., Phillips R. A., Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell. 1985 Aug;42(1):71–79. doi: 10.1016/s0092-8674(85)80102-1. [DOI] [PubMed] [Google Scholar]
  7. Ezine S., Weissman I. L., Rouse R. V. Bone marrow cells give rise to distinct cell clones within the thymus. Nature. 1984 Jun 14;309(5969):629–631. doi: 10.1038/309629a0. [DOI] [PubMed] [Google Scholar]
  8. Garman R. D., Doherty P. J., Raulet D. H. Diversity, rearrangement, and expression of murine T cell gamma genes. Cell. 1986 Jun 6;45(5):733–742. doi: 10.1016/0092-8674(86)90787-7. [DOI] [PubMed] [Google Scholar]
  9. Karagogeos D., Rosenberg N., Wortis H. H. Early arrest of B cell development in nude, X-linked immune-deficient mice. Eur J Immunol. 1986 Sep;16(9):1125–1130. doi: 10.1002/eji.1830160916. [DOI] [PubMed] [Google Scholar]
  10. Koyasu S., Yodoi J., Nikaido T., Tagaya Y., Taniguchi Y., Honjo T., Yahara I. Expression of interleukin 2 receptors on interleukin 3-dependent cell lines. J Immunol. 1986 Feb 1;136(3):984–987. [PubMed] [Google Scholar]
  11. 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]
  12. Le Gros G. S., Gillis S., Watson J. D. Induction of IL 2 responsiveness in a murine IL 3-dependent cell line. J Immunol. 1985 Dec;135(6):4009–4014. [PubMed] [Google Scholar]
  13. Lemischka I. R., Raulet D. H., Mulligan R. C. Developmental potential and dynamic behavior of hematopoietic stem cells. Cell. 1986 Jun 20;45(6):917–927. doi: 10.1016/0092-8674(86)90566-0. [DOI] [PubMed] [Google Scholar]
  14. Lesley J., Hyman R., Schulte R. Evidence that the Pgp-1 glycoprotein is expressed on thymus-homing progenitor cells of the thymus. Cell Immunol. 1985 Apr 1;91(2):397–403. doi: 10.1016/0008-8749(85)90237-0. [DOI] [PubMed] [Google Scholar]
  15. Moore M. A., Owen J. J. Experimental studies on the development of the thymus. J Exp Med. 1967 Oct 1;126(4):715–726. doi: 10.1084/jem.126.4.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mulder A. H., Visser J. W., van den Engh G. J. Thymus regeneration by bone marrow cell suspensions differing in the potential to form early and late spleen colonies. Exp Hematol. 1985 Sep;13(8):768–775. [PubMed] [Google Scholar]
  17. Möller G. Henry Kunkel. 1916-1983. Immunol Rev. 1984 Apr;78:5–6. [PubMed] [Google Scholar]
  18. Noma Y., Sideras P., Naito T., Bergstedt-Lindquist S., Azuma C., Severinson E., Tanabe T., Kinashi T., Matsuda F., Yaoita Y. Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature. 1986 Feb 20;319(6055):640–646. doi: 10.1038/319640a0. [DOI] [PubMed] [Google Scholar]
  19. Palacios R., Leu T. Both cloned interleukin 2 and purified interleukin 1 are required for optimal growth of purified L3T4+ and Lyt 2+ lymphocytes initiated by concanavalin A. Cell Immunol. 1985 Sep;94(2):369–382. doi: 10.1016/0008-8749(85)90261-8. [DOI] [PubMed] [Google Scholar]
  20. Palacios R., Leu T. CC11: a monoclonal antibody specific for interleukin 3-sensitive mouse cells defines two major populations of B cell precursors in the bone marrow. Immunol Rev. 1986 Oct;93:125–146. doi: 10.1111/j.1600-065x.1986.tb01505.x. [DOI] [PubMed] [Google Scholar]
  21. Palacios R., Neri T., Brockhaus M. Monoclonal antibodies specific for interleukin 3-sensitive murine cells. J Exp Med. 1986 Feb 1;163(2):369–382. doi: 10.1084/jem.163.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Palacios R., Von Boehmer H. Requirements for growth of immature thymocytes from fetal and adult mice in vitro. Eur J Immunol. 1986 Jan;16(1):12–19. doi: 10.1002/eji.1830160104. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Robb R. J., Greene W. C., Rusk C. M. Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen. J Exp Med. 1984 Oct 1;160(4):1126–1146. doi: 10.1084/jem.160.4.1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Roehm N., Herron L., Cambier J., DiGuisto D., Haskins K., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells: distribution on thymus and peripheral T cells. Cell. 1984 Sep;38(2):577–584. doi: 10.1016/0092-8674(84)90512-9. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Sakaguchi N., Berger C. N., Melchers F. Isolation of a cDNA copy of an RNA species expressed in murine pre-B cells. EMBO J. 1986 Sep;5(9):2139–2147. doi: 10.1002/j.1460-2075.1986.tb04477.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Saracci R., Repetto F. Time trends of primary liver cancer: indication of increased incidence in selected cancer registry populations. J Natl Cancer Inst. 1980 Aug;65(2):241–247. [PubMed] [Google Scholar]
  30. Sideras P., Palacios R. Bone marrow pro-T and pro-B lymphocyte clones express functional receptors for interleukin (IL) 3 and IL 4/BSF-1 and nonfunctional receptors for IL 2. Eur J Immunol. 1987 Feb;17(2):217–221. doi: 10.1002/eji.1830170211. [DOI] [PubMed] [Google Scholar]
  31. Snodgrass H. R., Dembić Z., Steinmetz M., von Boehmer H. Expression of T-cell antigen receptor genes during fetal development in the thymus. Nature. 1985 May 16;315(6016):232–233. doi: 10.1038/315232a0. [DOI] [PubMed] [Google Scholar]
  32. Snodgrass H. R., Kisielow P., Kiefer M., Steinmetz M., von Boehmer H. Ontogeny of the T-cell antigen receptor within the thymus. Nature. 1985 Feb 14;313(6003):592–595. doi: 10.1038/313592a0. [DOI] [PubMed] [Google Scholar]
  33. Traunecker A., Kiefer M., Dembić Z., Steinmetz M., Karjalainen K. Rearrangements of T cell receptor loci can be found only rarely in B lymphoid cells. Eur J Immunol. 1986 Apr;16(4):430–434. doi: 10.1002/eji.1830160420. [DOI] [PubMed] [Google Scholar]
  34. Traunecker A., Oliveri F., Allen N., Karjalainen K. Normal T cell development is possible without 'functional' gamma chain genes. EMBO J. 1986 Jul;5(7):1589–1593. doi: 10.1002/j.1460-2075.1986.tb04400.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Trowbridge I. S., Lesley J., Schulte R., Hyman R., Trotter J. Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues. Immunogenetics. 1982 Mar;15(3):299–312. doi: 10.1007/BF00364338. [DOI] [PubMed] [Google Scholar]
  36. Vetvicka V., Kincade P. W., Witte P. L. Effects of 5-fluorouracil on B lymphocyte lineage cells. J Immunol. 1986 Oct 15;137(8):2405–2410. [PubMed] [Google Scholar]
  37. Wu A. M., Till J. E., Siminovitch L., McCulloch E. A. A cytological study of the capacity for differentiation of normal hemopoietic colony-forming cells. J Cell Physiol. 1967 Apr;69(2):177–184. doi: 10.1002/jcp.1040690208. [DOI] [PubMed] [Google Scholar]
  38. Yokota T., Lee F., Rennick D., Hall C., Arai N., Mosmann T., Nabel G., Cantor H., Arai K. Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1070–1074. doi: 10.1073/pnas.81.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]

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