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. 1989 Jun;9(6):2665–2671. doi: 10.1128/mcb.9.6.2665

Identification of a novel bone marrow-derived B-cell progenitor population that coexpresses B220 and Thy-1 and is highly enriched for Abelson leukemia virus targets.

G F Tidmarsh 1, S Heimfeld 1, C A Whitlock 1, I L Weissman 1, C E Müller-Sieburg 1
PMCID: PMC362339  PMID: 2474759

Abstract

A novel stage in early B-lymphocyte differentiation has been identified in normal mouse bone marrow cells. Earlier work had demonstrated that bone marrow cells characterized by low levels of Thy-1 and lack of a panel of lineage markers (Thy-1lo Lin- cells) were highly enriched for pluripotent hematopoietic stem cells. In this paper, we present evidence that another bone marrow population, which expressed low levels of Thy-1 and coexpressed B220, a B-lineage-specific form of the leukocyte common antigen, contained early and potent precursors for B lymphocytes upon in vivo transfer to irradiated hosts. These Thy-1lo B220+ cells, comprising 1 to 2% of bone marrow cells, were enriched for large cells in the mitotic cycle; the population lacked significant pluripotent hematopoietic stem cell activity and myeloid-erythroid progenitors. Most strikingly, Thy-1lo B220+ cells represented a highly enriched population of bone marrow cells that could be targets of Abelson murine leukemia virus transformation. We propose that Thy-1lo B220+ bone marrow cells represent the earliest stage of committed lymphocyte progenitors, intermediate in differentiation between Thy-1lo Lin- pluripotent stem cells and, in the B lineage, Thy-1- B220+ pre-B cells.

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Selected References

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  1. Abelson H. T., Rabstein L. S. Lymphosarcoma: virus-induced thymic-independent disease in mice. Cancer Res. 1970 Aug;30(8):2213–2222. [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., Yancopoulos G. D., Blackwell T. K., Wood C., Thomas E., Boss M., Coffman R., Rosenberg N., Tonegawa S., Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984 Jun;3(6):1209–1219. doi: 10.1002/j.1460-2075.1984.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Alt F., Rosenberg N., Lewis S., Thomas E., Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes. Cell. 1981 Dec;27(2 Pt 1):381–390. doi: 10.1016/0092-8674(81)90421-9. [DOI] [PubMed] [Google Scholar]
  5. Basch R. S., Berman J. W. Thy-1 determinants are present on many murine hematopoietic cells other than T cells. Eur J Immunol. 1982 May;12(5):359–364. doi: 10.1002/eji.1830120502. [DOI] [PubMed] [Google Scholar]
  6. Boss M., Greaves M., Teich N. Abelson virus-transformed haematopoietic cell lines with pre-B-cell characteristics. Nature. 1979 Apr 5;278(5704):551–553. doi: 10.1038/278551a0. [DOI] [PubMed] [Google Scholar]
  7. Burrows P. D., Kearney J. F., Lawton A. R., Cooper M. D. Pre-B cells: bone marrow persistence in anti-mu-suppressed mice, conversion to B lymphocytes, and recovery after destruction by cyclophosphamide. J Immunol. 1978 May;120(5):1526–1531. [PubMed] [Google Scholar]
  8. Coffman R. L. Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development. Immunol Rev. 1982;69:5–23. doi: 10.1111/j.1600-065x.1983.tb00446.x. [DOI] [PubMed] [Google Scholar]
  9. Coffman R. L., Weissman I. L. B220: a B cell-specific member of th T200 glycoprotein family. Nature. 1981 Feb 19;289(5799):681–683. doi: 10.1038/289681a0. [DOI] [PubMed] [Google Scholar]
  10. Coffman R. L., Weissman I. L. Immunoglobulin gene rearrangement during pre-B cell differentiation. J Mol Cell Immunol. 1983;1(1):31–41. [PubMed] [Google Scholar]
  11. 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]
  12. Cook W. D. Rapid thymomas induced by Abelson murine leukemia virus. Proc Natl Acad Sci U S A. 1982 May;79(9):2917–2921. doi: 10.1073/pnas.79.9.2917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  14. Gunter K. C., Malek T. R., Shevach E. M. T cell-activating properties of an anti-Thy-1 monoclonal antibody. Possible analogy to OKT3/Leu-4. J Exp Med. 1984 Mar 1;159(3):716–730. doi: 10.1084/jem.159.3.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Herzenberg L. A., Stall A. M., Lalor P. A., Sidman C., Moore W. A., Parks D. R., Herzenberg L. A. The Ly-1 B cell lineage. Immunol Rev. 1986 Oct;93:81–102. doi: 10.1111/j.1600-065x.1986.tb01503.x. [DOI] [PubMed] [Google Scholar]
  16. Imaizumi A., Terada S., Kimoto E. Monoclonal anti-Thy-1.2 antibody induced hematopoiesis in vivo. Leuk Res. 1988;12(1):45–50. doi: 10.1016/s0145-2126(98)80007-6. [DOI] [PubMed] [Google Scholar]
  17. Konaka Y., Norcross M. A., Maino V. C., Smith R. T. Anti-Thy-1-mediated T cell activation. Role of soluble factors and expression of interleukin 2 receptors on T cells. Eur J Immunol. 1981 Jun;11(6):445–450. doi: 10.1002/eji.1830110602. [DOI] [PubMed] [Google Scholar]
  18. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  19. Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
  20. McGrath M. S., Pillemer E., Weissman I. L. Murine leukaemogenesis: monoclonal antibodies to T-cell determinants arrest T-lymphoma cell proliferation. Nature. 1980 May 22;285(5762):259–261. doi: 10.1038/285259a0. [DOI] [PubMed] [Google Scholar]
  21. Muller-Sieburg C. E., Whitlock C. A., Weissman I. L. Isolation of two early B lymphocyte progenitors from mouse marrow: a committed pre-pre-B cell and a clonogenic Thy-1-lo hematopoietic stem cell. Cell. 1986 Feb 28;44(4):653–662. doi: 10.1016/0092-8674(86)90274-6. [DOI] [PubMed] [Google Scholar]
  22. Müller-Sieburg C. E., Tidmarsh G. F., Weissman I. L., Spangrude G. J. Maturation of hematolymphoid cells that express Thy-1. Immunol Ser. 1989;45:289–316. [PubMed] [Google Scholar]
  23. Müller-Sieburg C. E., Townsend K., Weissman I. L., Rennick D. Proliferation and differentiation of highly enriched mouse hematopoietic stem cells and progenitor cells in response to defined growth factors. J Exp Med. 1988 Jun 1;167(6):1825–1840. doi: 10.1084/jem.167.6.1825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nottenburg C., Weissman I. L. Cmu gene rearrangement of mouse immunoglobulin genes in normal B cells occurs on both the expressed and nonexpressed chromosomes. Proc Natl Acad Sci U S A. 1981 Jan;78(1):484–488. doi: 10.1073/pnas.78.1.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  26. Osmond D. G., Nossal G. J. Differentiation of lymphocytes in mouse bone marrow. II. Kinetics of maturation and renewal of antiglobulin-binding cells studied by double labeling. Cell Immunol. 1974 Jul;13(1):132–145. doi: 10.1016/0008-8749(74)90233-0. [DOI] [PubMed] [Google Scholar]
  27. Pillemer E., Whitlock C., Weissman I. L. Transformation-associated proteins in murine B-cell lymphomas that are distinct from Abelson virus gene products. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4434–4438. doi: 10.1073/pnas.81.14.4434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Raff M. C., Megson M., Owen J. J., Cooper M. D. Early production of intracellular IgM by B-lymphocyte precursors in mouse. Nature. 1976 Jan 22;259(5540):224–226. doi: 10.1038/259224a0. [DOI] [PubMed] [Google Scholar]
  29. Raschke W. C., Baird S., Ralph P., Nakoinz I. Functional macrophage cell lines transformed by Abelson leukemia virus. Cell. 1978 Sep;15(1):261–267. doi: 10.1016/0092-8674(78)90101-0. [DOI] [PubMed] [Google Scholar]
  30. Rosenberg N. Abelson leukemia virus. Curr Top Microbiol Immunol. 1982;101:95–126. doi: 10.1007/978-3-642-68654-2_5. [DOI] [PubMed] [Google Scholar]
  31. Rosenberg N., Baltimore D. A quantitative assay for transformation of bone marrow cells by Abelson murine leukemia virus. J Exp Med. 1976 Jun 1;143(6):1453–1463. doi: 10.1084/jem.143.6.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rosenberg N., Baltimore D., Scher C. D. In vitro transformation of lymphoid cells by Abelson murine leukemia virus. Proc Natl Acad Sci U S A. 1975 May;72(5):1932–1936. doi: 10.1073/pnas.72.5.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Scheid M. P., Landreth K. S., Tung J. S., Kincade P. W. Preferential but nonexclusive expression of macromolecular antigens on B-lineage cells. Immunol Rev. 1982;69:141–159. doi: 10.1111/j.1600-065x.1983.tb00453.x. [DOI] [PubMed] [Google Scholar]
  34. Scher C. D., Siegler R. Direct transformation of 3T3 cells by Abelson murine leukaemia virus. Nature. 1975 Feb 27;253(5494):729–731. doi: 10.1038/253729a0. [DOI] [PubMed] [Google Scholar]
  35. Shinefeld L. A., Sato V. L., Rosenberg N. E. Monoclonal rat anti-mouse brain antibody detects Abelson murine leukemia virus target cells in mouse bone marrow. Cell. 1980 May;20(1):11–17. doi: 10.1016/0092-8674(80)90229-9. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Spangrude G. J., Heimfeld S., Weissman I. L. Purification and characterization of mouse hematopoietic stem cells. Science. 1988 Jul 1;241(4861):58–62. doi: 10.1126/science.2898810. [DOI] [PubMed] [Google Scholar]
  38. Spangrude G. J., Muller-Sieburg C. E., Heimfeld S., Weissman I. L. Two rare populations of mouse Thy-1lo bone marrow cells repopulate the thymus. J Exp Med. 1988 May 1;167(5):1671–1683. doi: 10.1084/jem.167.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
  40. TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]
  41. Tidmarsh G. F., Dailey M. O., Whitlock C. A., Pillemer E., Weissman I. L. Transformed lymphocytes from Abelson-diseased mice express levels of a B lineage transformation-associated antigen elevated from that found on normal lymphocytes. J Exp Med. 1985 Nov 1;162(5):1421–1434. doi: 10.1084/jem.162.5.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Waneck G. L., Rosenberg N. Abelson leukemia virus induces lymphoid and erythroid colonies in infected fetal cell cultures. Cell. 1981 Oct;26(1 Pt 1):79–89. doi: 10.1016/0092-8674(81)90035-0. [DOI] [PubMed] [Google Scholar]
  43. Whitlock C. A., Tidmarsh G. F., Muller-Sieburg C., Weissman I. L. Bone marrow stromal cell lines with lymphopoietic activity express high levels of a pre-B neoplasia-associated molecule. Cell. 1987 Mar 27;48(6):1009–1021. doi: 10.1016/0092-8674(87)90709-4. [DOI] [PubMed] [Google Scholar]

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