Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1996 Aug 1;15(15):3823–3834.

Progenitor tumours from Emu-bcl-2-myc transgenic mice have lymphomyeloid differentiation potential and reveal developmental differences in cell survival.

A Strasser 1, A G Elefanty 1, A W Harris 1, S Cory 1
PMCID: PMC452067  PMID: 8670887

Abstract

Mice expressing both a bcl-2 and a myc transgene within the B lymphoid cell compartment invariably develop novel immature haemopoietic tumours. The likely cell of origin of these tumours was identified by a common pattern of cell surface marker expression on a subset of cells comprising approximately 1% of normal mouse bone marrow. The bcl-2-myc tumour cells could be induced to differentiate into either B lymphocytes or macrophages in culture with certain cytokines and feeder cells. Analysis of their progression into the B lymphoid lineage revealed that Igk locus transcription can precede Igh as well as Igk rearrangement. Surprisingly, the undifferentiated tumour cells died rapidly in culture, even in the presence of multiple cytokines, but they proliferated on monolayers of stromal cells derived from haemopoietic tissues. Thus, even with Bcl-2 levels that protect more differentiated cells, these immature bi-potential progenitor cells require a stromal-induced signal for survival. These results provide insight into the process of lineage commitment and suggest new levels of control of cell survival during early steps in haemopoietic development.

Full text

PDF
3823

Images in this article

3826Image
on p.3826
3826Image
on p.3826
3828Image
on p.3828
3830Image
on p.3830

Selected References

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

  1. Adams J. M., Harris A. W., Pinkert C. A., Corcoran L. M., Alexander W. S., Cory S., Palmiter R. D., Brinster R. L. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985 Dec 12;318(6046):533–538. doi: 10.1038/318533a0. [DOI] [PubMed] [Google Scholar]
  2. Askew D. S., Ashmun R. A., Simmons B. C., Cleveland J. L. Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene. 1991 Oct;6(10):1915–1922. [PubMed] [Google Scholar]
  3. Ayroldi E., Cannarile L., Migliorati G., Bartoli A., Nicoletti I., Riccardi C. CD44 (Pgp-1) inhibits CD3 and dexamethasone-induced apoptosis. Blood. 1995 Oct 1;86(7):2672–2678. [PubMed] [Google Scholar]
  4. Bauer S. R., Holmes K. L., Morse H. C., 3rd, Potter M. Clonal relationship of the lymphoblastic cell line P388 to the macrophage cell line P388D1 as evidenced by immunoglobulin gene rearrangements and expression of cell surface antigens. J Immunol. 1986 Jun 15;136(12):4695–4699. [PubMed] [Google Scholar]
  5. Berenson R. J., Andrews R. G., Bensinger W. I., Kalamasz D., Knitter G., Buckner C. D., Bernstein I. D. Antigen CD34+ marrow cells engraft lethally irradiated baboons. J Clin Invest. 1988 Mar;81(3):951–955. doi: 10.1172/JCI113409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Borzillo G. V., Ashmun R. A., Sherr C. J. Macrophage lineage switching of murine early pre-B lymphoid cells expressing transduced fms genes. Mol Cell Biol. 1990 Jun;10(6):2703–2714. doi: 10.1128/mcb.10.6.2703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Boyd A. W., Schrader J. W. Derivation of macrophage-like lines from the pre-B lymphoma ABLS 8.1 using 5-azacytidine. Nature. 1982 Jun 24;297(5868):691–693. doi: 10.1038/297691a0. [DOI] [PubMed] [Google Scholar]
  8. Christofori G., Naik P., Hanahan D. A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis. Nature. 1994 Jun 2;369(6479):414–418. doi: 10.1038/369414a0. [DOI] [PubMed] [Google Scholar]
  9. Corcoran L. M., Karvelas M., Nossal G. J., Ye Z. S., Jacks T., Baltimore D. Oct-2, although not required for early B-cell development, is critical for later B-cell maturation and for postnatal survival. Genes Dev. 1993 Apr;7(4):570–582. doi: 10.1101/gad.7.4.570. [DOI] [PubMed] [Google Scholar]
  10. Cory S. Regulation of lymphocyte survival by the bcl-2 gene family. Annu Rev Immunol. 1995;13:513–543. doi: 10.1146/annurev.iy.13.040195.002501. [DOI] [PubMed] [Google Scholar]
  11. Cumano A., Paige C. J., Iscove N. N., Brady G. Bipotential precursors of B cells and macrophages in murine fetal liver. Nature. 1992 Apr 16;356(6370):612–615. doi: 10.1038/356612a0. [DOI] [PubMed] [Google Scholar]
  12. Davidson W. F., Pierce J. H., Rudikoff S., Morse H. C., 3rd Relationships between B cell and myeloid differentiation. Studies with a B lymphocyte progenitor line, HAFTL-1. J Exp Med. 1988 Jul 1;168(1):389–407. doi: 10.1084/jem.168.1.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dexter T. M., Allen T. D., Lajtha L. G. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977 Jun;91(3):335–344. doi: 10.1002/jcp.1040910303. [DOI] [PubMed] [Google Scholar]
  14. Ehlich A., Schaal S., Gu H., Kitamura D., Müller W., Rajewsky K. Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development. Cell. 1993 Mar 12;72(5):695–704. doi: 10.1016/0092-8674(93)90398-a. [DOI] [PubMed] [Google Scholar]
  15. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  16. Fanidi A., Harrington E. A., Evan G. I. Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature. 1992 Oct 8;359(6395):554–556. doi: 10.1038/359554a0. [DOI] [PubMed] [Google Scholar]
  17. Francés V., Pandrau-Garcia D., Guret C., Ho S., Wang Z., Duvert V., Saeland S., Martinez-Valdez H. A surrogate 15 kDa JC kappa protein is expressed in combination with mu heavy chain by human B cell precursors. EMBO J. 1994 Dec 15;13(24):5937–5943. doi: 10.1002/j.1460-2075.1994.tb06939.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Frederickson G. G., Basch R. S. L3T4 antigen expression by hemopoietic precursor cells. J Exp Med. 1989 Apr 1;169(4):1473–1478. doi: 10.1084/jem.169.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gimble J. M., Dorheim M. A., Cheng Q., Medina K., Wang C. S., Jones R., Koren E., Pietrangeli C., Kincade P. W. Adipogenesis in a murine bone marrow stromal cell line capable of supporting B lineage lymphocyte growth and proliferation: biochemical and molecular characterization. Eur J Immunol. 1990 Feb;20(2):379–387. doi: 10.1002/eji.1830200222. [DOI] [PubMed] [Google Scholar]
  20. Grabstein K. H., Waldschmidt T. J., Finkelman F. D., Hess B. W., Alpert A. R., Boiani N. E., Namen A. E., Morrissey P. J. Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody. J Exp Med. 1993 Jul 1;178(1):257–264. doi: 10.1084/jem.178.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Grawunder U., Haasner D., Melchers F., Rolink A. Rearrangement and expression of kappa light chain genes can occur without mu heavy chain expression during differentiation of pre-B cells. Int Immunol. 1993 Dec;5(12):1609–1618. doi: 10.1093/intimm/5.12.1609. [DOI] [PubMed] [Google Scholar]
  22. Hanecak R., Zovich D. C., Pattengale P. K., Fan H. Differentiation in vitro of a leukemia virus-induced B-cell lymphoma into macrophages. Mol Cell Biol. 1989 May;9(5):2264–2268. doi: 10.1128/mcb.9.5.2264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Harrington E. A., Bennett M. R., Fanidi A., Evan G. I. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 1994 Jul 15;13(14):3286–3295. doi: 10.1002/j.1460-2075.1994.tb06630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Harris A. W., Pinkert C. A., Crawford M., Langdon W. Y., Brinster R. L., Adams J. M. The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells. J Exp Med. 1988 Feb 1;167(2):353–371. doi: 10.1084/jem.167.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hayashi S., Kunisada T., Ogawa M., Sudo T., Kodama H., Suda T., Nishikawa S., Nishikawa S. Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules. J Exp Med. 1990 May 1;171(5):1683–1695. doi: 10.1084/jem.171.5.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hermanson G. G., Eisenberg D., Kincade P. W., Wall R. B29: a member of the immunoglobulin gene superfamily exclusively expressed on beta-lineage cells. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6890–6894. doi: 10.1073/pnas.85.18.6890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Herr W., Sturm R. A., Clerc R. G., Corcoran L. M., Baltimore D., Sharp P. A., Ingraham H. A., Rosenfeld M. G., Finney M., Ruvkun G. The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev. 1988 Dec;2(12A):1513–1516. doi: 10.1101/gad.2.12a.1513. [DOI] [PubMed] [Google Scholar]
  28. Hirayama F., Lyman S. D., Clark S. C., Ogawa M. The flt3 ligand supports proliferation of lymphohematopoietic progenitors and early B-lymphoid progenitors. Blood. 1995 Apr 1;85(7):1762–1768. [PubMed] [Google Scholar]
  29. Jacobsen K. A., Prasad V. S., Sidman C. L., Osmond D. G. Apoptosis and macrophage-mediated deletion of precursor B cells in the bone marrow of E mu-myc transgenic mice. Blood. 1994 Oct 15;84(8):2784–2794. [PubMed] [Google Scholar]
  30. Karasuyama H., Melchers F. Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors. Eur J Immunol. 1988 Jan;18(1):97–104. doi: 10.1002/eji.1830180115. [DOI] [PubMed] [Google Scholar]
  31. Kee B. L., Cumano A., Iscove N. N., Paige C. J. Stromal cell independent growth of bipotent B cell--macrophage precursors from murine fetal liver. Int Immunol. 1994 Mar;6(3):401–407. doi: 10.1093/intimm/6.3.401. [DOI] [PubMed] [Google Scholar]
  32. Klinken S. P., Alexander W. S., Adams J. M. Hemopoietic lineage switch: v-raf oncogene converts Emu-myc transgenic B cells into macrophages. Cell. 1988 Jun 17;53(6):857–867. doi: 10.1016/s0092-8674(88)90309-1. [DOI] [PubMed] [Google Scholar]
  33. Klug C. A., Gerety S. J., Shah P. C., Chen Y. Y., Rice N. R., Rosenberg N., Singh H. The v-abl tyrosine kinase negatively regulates NF-kappa B/Rel factors and blocks kappa gene transcription in pre-B lymphocytes. Genes Dev. 1994 Mar 15;8(6):678–687. doi: 10.1101/gad.8.6.678. [DOI] [PubMed] [Google Scholar]
  34. Koopman G., Keehnen R. M., Lindhout E., Newman W., Shimizu Y., van Seventer G. A., de Groot C., Pals S. T. Adhesion through the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and the VLA-4 (CD49d)-VCAM-1 (CD106) pathways prevents apoptosis of germinal center B cells. J Immunol. 1994 Apr 15;152(8):3760–3767. [PubMed] [Google Scholar]
  35. Krause D. S., Ito T., Fackler M. J., Smith O. M., Collector M. I., Sharkis S. J., May W. S. Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells. Blood. 1994 Aug 1;84(3):691–701. [PubMed] [Google Scholar]
  36. Kubagawa H., Cooper M. D., Carroll A. J., Burrows P. D. Light-chain gene expression before heavy-chain gene rearrangement in pre-B cells transformed by Epstein-Barr virus. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2356–2360. doi: 10.1073/pnas.86.7.2356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Landreth K. S., Narayanan R., Dorshkind K. Insulin-like growth factor-I regulates pro-B cell differentiation. Blood. 1992 Sep 1;80(5):1207–1212. [PubMed] [Google Scholar]
  38. Langdon W. Y., Harris A. W., Cory S., Adams J. M. The c-myc oncogene perturbs B lymphocyte development in E-mu-myc transgenic mice. Cell. 1986 Oct 10;47(1):11–18. doi: 10.1016/0092-8674(86)90361-2. [DOI] [PubMed] [Google Scholar]
  39. Langdon W. Y., Harris A. W., Cory S. Growth of E mu-myc transgenic B-lymphoid cells in vitro and their evolution toward autonomy. Oncogene Res. 1988;3(3):271–279. [PubMed] [Google Scholar]
  40. Leclercq L., Butkeraitis P., Reth M. A novel germ-line JK transcript starting immediately upstream of JK1. Nucleic Acids Res. 1989 Sep 12;17(17):6809–6819. doi: 10.1093/nar/17.17.6809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lee K. H., Kinashi T., Tohyama K., Tashiro K., Funato N., Hama K., Honjo T. Different stromal cell lines support lineage-selective differentiation of the multipotential bone marrow stem cell clone LyD9. J Exp Med. 1991 May 1;173(5):1257–1266. doi: 10.1084/jem.173.5.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lennon G. G., Perry R. P. C mu-containing transcripts initiate heterogeneously within the IgH enhancer region and contain a novel 5'-nontranslatable exon. Nature. 1985 Dec 5;318(6045):475–478. doi: 10.1038/318475a0. [DOI] [PubMed] [Google Scholar]
  43. Leung L. C., Johnson G. R. In vitro maintenance of hemopoietic stem cells with lymphoid and myeloid repopulating ability by a cloned murine adherent bone marrow cell line. Exp Hematol. 1987 Oct;15(9):989–994. [PubMed] [Google Scholar]
  44. Li Y. S., Hayakawa K., Hardy R. R. The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. J Exp Med. 1993 Sep 1;178(3):951–960. doi: 10.1084/jem.178.3.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Lindeman G. J., Adams J. M., Cory S., Harris A. W. B-lymphoid to granulocytic switch during hematopoiesis in a transgenic mouse strain. Immunity. 1994 Sep;1(6):517–527. doi: 10.1016/1074-7613(94)90094-9. [DOI] [PubMed] [Google Scholar]
  46. Martin D. J., van Ness B. G. Initiation and processing of two kappa immunoglobulin germ line transcripts in mouse B cells. Mol Cell Biol. 1990 May;10(5):1950–1958. doi: 10.1128/mcb.10.5.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Martin M., Strasser A., Baumgarth N., Cicuttini F. M., Welch K., Salvaris E., Boyd A. W. A novel cellular model (SPGM 1) of switching between the pre-B cell and myelomonocytic lineages. J Immunol. 1993 May 15;150(10):4395–4406. [PubMed] [Google Scholar]
  48. Matthews W., Jordan C. T., Wiegand G. W., Pardoll D., Lemischka I. R. A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations. Cell. 1991 Jun 28;65(7):1143–1152. doi: 10.1016/0092-8674(91)90010-v. [DOI] [PubMed] [Google Scholar]
  49. McDonnell T. J., Deane N., Platt F. M., Nunez G., Jaeger U., McKearn J. P., Korsmeyer S. J. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989 Apr 7;57(1):79–88. doi: 10.1016/0092-8674(89)90174-8. [DOI] [PubMed] [Google Scholar]
  50. McDonnell T. J., Korsmeyer S. J. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. 1991 Jan 17;349(6306):254–256. doi: 10.1038/349254a0. [DOI] [PubMed] [Google Scholar]
  51. Mufti G. J., Hamblin T. J., Oscier D. G., Johnson S. Common ALL with pre-B-cell features showing (8;14) and (14;18) chromosome translocations. Blood. 1983 Nov;62(5):1142–1146. [PubMed] [Google Scholar]
  52. 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]
  53. Nelson K. J., Kelley D. E., Perry R. P. Inducible transcription of the unrearranged kappa constant region locus is a common feature of pre-B cells and does not require DNA or protein synthesis. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5305–5309. doi: 10.1073/pnas.82.16.5305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Ogawa M. Differentiation and proliferation of hematopoietic stem cells. Blood. 1993 Jun 1;81(11):2844–2853. [PubMed] [Google Scholar]
  55. Okada S., Nakauchi H., Nagayoshi K., Nishikawa S., Nishikawa S., Miura Y., Suda T. Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule. Blood. 1991 Oct 1;78(7):1706–1712. [PubMed] [Google Scholar]
  56. Palacios R., Karasuyama H., Rolink A. Ly1+ PRO-B lymphocyte clones. Phenotype, growth requirements and differentiation in vitro and in vivo. EMBO J. 1987 Dec 1;6(12):3687–3693. doi: 10.1002/j.1460-2075.1987.tb02702.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Principato M., Cleveland J. L., Rapp U. R., Holmes K. L., Pierce J. H., Morse H. C., 3rd, Klinken S. P. Transformation of murine bone marrow cells with combined v-raf-v-myc oncogenes yields clonally related mature B cells and macrophages. Mol Cell Biol. 1990 Jul;10(7):3562–3568. doi: 10.1128/mcb.10.7.3562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Reth M., Petrac E., Wiese P., Lobel L., Alt F. W. Activation of V kappa gene rearrangement in pre-B cells follows the expression of membrane-bound immunoglobulin heavy chains. EMBO J. 1987 Nov;6(11):3299–3305. doi: 10.1002/j.1460-2075.1987.tb02649.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Rolink A., Karasuyama H., Haasner D., Grawunder U., Mårtensson I. L., Kudo A., Melchers F. Two pathways of B-lymphocyte development in mouse bone marrow and the roles of surrogate L chain in this development. Immunol Rev. 1994 Feb;137:185–201. doi: 10.1111/j.1600-065x.1994.tb00665.x. [DOI] [PubMed] [Google Scholar]
  60. Rolink A., ten Boekel E., Melchers F., Fearon D. T., Krop I., Andersson J. A subpopulation of B220+ cells in murine bone marrow does not express CD19 and contains natural killer cell progenitors. J Exp Med. 1996 Jan 1;183(1):187–194. doi: 10.1084/jem.183.1.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Sakaguchi N., Kashiwamura S., Kimoto M., Thalmann P., Melchers F. B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties. EMBO J. 1988 Nov;7(11):3457–3464. doi: 10.1002/j.1460-2075.1988.tb03220.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Schatz D. G., Oettinger M. A., Schlissel M. S. V(D)J recombination: molecular biology and regulation. Annu Rev Immunol. 1992;10:359–383. doi: 10.1146/annurev.iy.10.040192.002043. [DOI] [PubMed] [Google Scholar]
  63. Schlissel M. S., Baltimore D. Activation of immunoglobulin kappa gene rearrangement correlates with induction of germline kappa gene transcription. Cell. 1989 Sep 8;58(5):1001–1007. doi: 10.1016/0092-8674(89)90951-3. [DOI] [PubMed] [Google Scholar]
  64. 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]
  65. Strasser A., Harris A. W., Bath M. L., Cory S. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature. 1990 Nov 22;348(6299):331–333. doi: 10.1038/348331a0. [DOI] [PubMed] [Google Scholar]
  66. Strasser A., Harris A. W., Cory S. E mu-bcl-2 transgene facilitates spontaneous transformation of early pre-B and immunoglobulin-secreting cells but not T cells. Oncogene. 1993 Jan;8(1):1–9. [PubMed] [Google Scholar]
  67. Strasser A., Harris A. W., Cory S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 1991 Nov 29;67(5):889–899. doi: 10.1016/0092-8674(91)90362-3. [DOI] [PubMed] [Google Scholar]
  68. Strasser A., Harris A. W., Huang D. C., Krammer P. H., Cory S. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J. 1995 Dec 15;14(24):6136–6147. doi: 10.1002/j.1460-2075.1995.tb00304.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Strasser A., Whittingham S., Vaux D. L., Bath M. L., Adams J. M., Cory S., Harris A. W. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8661–8665. doi: 10.1073/pnas.88.19.8661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Szilvassy S. J., Cory S. Phenotypic and functional characterization of competitive long-term repopulating hematopoietic stem cells enriched from 5-fluorouracil-treated murine marrow. Blood. 1993 May 1;81(9):2310–2320. [PubMed] [Google Scholar]
  71. Taylor I. W. A rapid single step staining technique for DNA analysis by flow microfluorimetry. J Histochem Cytochem. 1980 Sep;28(9):1021–1024. doi: 10.1177/28.9.6157714. [DOI] [PubMed] [Google Scholar]
  72. Tsubata T., Tsubata R., Reth M. Crosslinking of the cell surface immunoglobulin (mu-surrogate light chains complex) on pre-B cells induces activation of V gene rearrangements at the immunoglobulin kappa locus. Int Immunol. 1992 Jun;4(6):637–641. doi: 10.1093/intimm/4.6.637. [DOI] [PubMed] [Google Scholar]
  73. Vaux D. L., Cory S., Adams J. M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 1988 Sep 29;335(6189):440–442. doi: 10.1038/335440a0. [DOI] [PubMed] [Google Scholar]
  74. Wagner A. J., Small M. B., Hay N. Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2. Mol Cell Biol. 1993 Apr;13(4):2432–2440. doi: 10.1128/mcb.13.4.2432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. 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]
  76. Wineman J. P., Gilmore G. L., Gritzmacher C., Torbett B. E., Müller-Sieburg C. E. CD4 is expressed on murine pluripotent hematopoietic stem cells. Blood. 1992 Oct 1;80(7):1717–1724. [PubMed] [Google Scholar]
  77. Winkler T. H., Melchers F., Rolink A. G. Interleukin-3 and interleukin-7 are alternative growth factors for the same B-cell precursors in the mouse. Blood. 1995 Apr 15;85(8):2045–2051. [PubMed] [Google Scholar]
  78. Witte O. N. Steel locus defines new multipotent growth factor. Cell. 1990 Oct 5;63(1):5–6. doi: 10.1016/0092-8674(90)90280-r. [DOI] [PubMed] [Google Scholar]
  79. Wu L., Scollay R., Egerton M., Pearse M., Spangrude G. J., Shortman K. CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus. Nature. 1991 Jan 3;349(6304):71–74. doi: 10.1038/349071a0. [DOI] [PubMed] [Google Scholar]
  80. Yancopoulos G. D., Alt F. W. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell. 1985 Feb;40(2):271–281. doi: 10.1016/0092-8674(85)90141-2. [DOI] [PubMed] [Google Scholar]

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

RESOURCES