B Cell Precursors in Bone Marrow: In Vivo Proliferation, Localization, Stimulation by Activated Macrophages and Implications for Oncogenesis

  • D. G. Osmond
  • Y.-H. Park
  • K. Jacobsen
Conference paper
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 141)


Precursor cells in mammalian bone marrow continuously give rise to virgin B lymphocytes by undergoing a series of genetic, mitotic and selection events (Osmond 1985, 1986, Osmond & Park 1987). During the differentiation of individual precursor cells the B cell antigen-binding specificities are determined by the formation of functional Ig variable (V) region genes from a combination of gene segments (Tonegawa 1983). The enzyme terminal deoxynucleotidyl transferase (TdT) can insert additional nucleotides during rearrangement of the heavy (H) chain gene, contributing to B cell diversity (Yancopoulos et al 1984, Kunkel et al 1986). Thereafter, however, the mitotic activity of the precursor B cells largely dictates the ultimate output of B cell clones, especially with respect to clone size (the number of B cells having a given antigen-binding specificity) and the number of different clones produced per unit time. This process may be modified by cell loss. The combined genetic and mitotic activities of early precursor B cells make them susceptible to genetic errors which may result in cell death. Other non-lethal aberrations could predispose to gene dysregul-ation and oncogenesis (Greaves 1986, Lenoir & Bornkum 1987, Harris et al 1988).


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  1. Batten DG & Osmond DG The localization of lymphocytres in mouse bone marrow: Radioautographic studies after in vivo perfusion of radiolabeled anti-IgM antibody. J Immunol Meth 72:381–399.Google Scholar
  2. Collins L, Dorshkind K (1987) A stromal cell line from myeloid long-term bone marrow cultures can support myelopoiesis and B lymphopoiesis. J Immunol 138:1082–1087PubMedGoogle Scholar
  3. Dorshkind K ((1986) In vitro differentiation of B lymphocytes from primitive hemopoietic precursors present in long-term bone marrow cultures. J Immunol 136:422–429PubMedGoogle Scholar
  4. Fulop GM & Osmond DG (1983) Regulation of bone marrow lymphocyte production. III Increased production of B and non-B lymphocytes after administering systemic antigens. Cell Immunol 75:80–90PubMedCrossRefGoogle Scholar
  5. Fulop GM, Pietrangeli CE & Osmond DG (1986) Regulation of bone marrow production. IV. Altered kinetic steady state of lymphocyte production after chronic changes in exogenous stimuli. Exp Hemat 14: 27–34.PubMedGoogle Scholar
  6. Greaves MF (1986) Differentiation-linked leukemogenesis in lymphocytes. Science 234:697–704PubMedCrossRefGoogle Scholar
  7. Harris AW, Pinkert CA, Crawford M, Langdon WY, Brinster, RL, Adams JM (1988) The E μ-myc transgenic mouse: A model for high-incidence spontaneous lymphoma and leukemia of early B cells. J Exp Med 167: 353–371PubMedCrossRefGoogle Scholar
  8. Kincade FW (1987) Experimental models for understanding B lymphocyte formation. Adv. Immunol 41:181–267PubMedCrossRefGoogle Scholar
  9. Kincade FW, Lee G, Watanabe T, Sun L and Scheid MP (1981) Antigens displayed on murine B lymphocyte precursors. J Immunol 127:2262–2268PubMedGoogle Scholar
  10. Klein G, Klein E (1986) Conditioned tumorigenicity of activated oncogenes. Cancer Res 46:3211–3224.PubMedGoogle Scholar
  11. Kqpriwa B (1975) A comparison of various procedures for fine grain development in electron microscope radioautography. Histochemie 44: 201–244.CrossRefGoogle Scholar
  12. Kunkel TA, Gopinathan KP, Dube KP, Snow ET and Loeb LA (1986) Rearrangements of DNA mediated by terminal transferase. Proc Nat Acad Sci USA 83:1867–1871PubMedCrossRefGoogle Scholar
  13. Landreth K, Dorshkind K (1988) Pre-B cell generation potentiated by soluble factors from a bone marrow stromal cell line. J Immunol 140: 845–852PubMedGoogle Scholar
  14. Langdon WY, Harris AW, Cory S, Adams JM (1986) The c-myc oncogene perturbs B lymphocyte development in Eμ-myc transgenic mice. Cell 47:11–18PubMedCrossRefGoogle Scholar
  15. Lenoir GM, Bornkum GW (1987) Burkitt’s lymphoma, a human cancer model for the study of the multistep model of cancer: proposal for a new scenario. Adv in Viral Oncology 7:173–206Google Scholar
  16. Namen AE, Schmierer AW, March CJ, Overell RW, Park LS, Urdal DL and Mochizuki DY (1988) B cell precursor growth-promoting activity. Purification and characterization of a growth factor active on lymphocyte precursors. J Exp Med 167:988–1002PubMedCrossRefGoogle Scholar
  17. Opstelten D & Osmond DG (1983) Pre-B cells in mouse bone marrow: immunofluorescence stathmokinetic studies of the proliferation of cytoplasmic μ chain-bearing cells in normal mice. J Immunol: 2635–2640Google Scholar
  18. Opstelten D & Osmond DG (1985) Regulation of pre-B cell proliferation in bone marrow: immunofluorescence stathmokinetic studies of cytoplasmic μ chain-bearing cells in anti-IgM-treated mice, hematologic-ally deficient mutant mice and mice given sheep red blood cells. Eur J Immunol 15:599–605PubMedCrossRefGoogle Scholar
  19. Osmond DG (1985) The ontogeny and organization of the lymphoid system. J Invest Dermatol 85:2s–9sPubMedCrossRefGoogle Scholar
  20. Osmond DG (1986) Population dynamics of bone marrow B lymphocytes. Immunol Rev 93:103–124PubMedCrossRefGoogle Scholar
  21. Osmond DG & Batten SJ (1984) Genesis of B lymphocytes in the bone marrow: Extravascular and intravascular localization of surface IgM-bearing cells in mouse bone marrow detected by electron microscope radioautography after in vivo perfusion of 125I anti-IgM antibody. Am J Anat 170:349–365PubMedCrossRefGoogle Scholar
  22. Osmond DG & Park YH (1987) B lymphocyte progenitors in mouse bone marrow. Int Rev Immunol 2:241–261PubMedCrossRefGoogle Scholar
  23. Park YH & Osmond DG (1987) Phenotype and proliferation of early precursor cells in mouse bone marrow. J Exp Med. 165:444–458.PubMedCrossRefGoogle Scholar
  24. Pietrangeli CE & Osmond DG (1985) Regulation of B-lymphocyte production in the bone marrow: Role of macrophages and the spleen in mediating responses to exogenous agents. Cell Immunol 94:147–158PubMedCrossRefGoogle Scholar
  25. Pietrangeli CE & Osmond DG (1987) Regulation of B lymphocyte production in the bone marrow: Mediation of the effects of exogenous stimulants by adoptively transferred spleen cells. Cell Immunol 107: 348–357PubMedCrossRefGoogle Scholar
  26. Potter M, Mushinski JF, Mushinski EV, Brust S, Wax JS, Wiener F, Babonits M, Rapp UR, Morse HC (1987) Avian v-myc replaces chromosomal translocation in murine plasmacytomagenesis. Science 235:787–789PubMedCrossRefGoogle Scholar
  27. Potter M, Wax JS, Anderson AO, Nordan RP (1985) Inhibition of plasmacytoma development in BALB/c mice by indomethacin. J Exp Med 161:996–1012PubMedCrossRefGoogle Scholar
  28. Tonegawa S (1983) Somatic generation of antibody diversity. Nature 302:575–581PubMedCrossRefGoogle Scholar
  29. Weiss L, Geduldig U, Weidanz W (1986) Mechanisms of splenic control of murine malaria: Reticular cell activation and the development of a blood-spleen barrier. Am J Anat 176:251–285PubMedCrossRefGoogle Scholar
  30. Whitlock CA, Robertson D, Witte ON (1984) Murine B cell lymphopoiesis in long term culture. J Immunol Meth 67:353–369.CrossRefGoogle Scholar
  31. Wyler DJ (1982) Malaria: Host-pathogen biology. Rev Infect Dis 4:785–797PubMedCrossRefGoogle Scholar
  32. Yancopoulos GD, Desiderio SV, Paskind M, Thomas E, Boss M, Landau N, Alt FW, Baltimore D (1984) Preferential utilization of the most J -proximal V gene segments in pre-B cell lines. Nature 311:727–733PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1988

Authors and Affiliations

  • D. G. Osmond
    • 1
  • Y.-H. Park
    • 1
  • K. Jacobsen
    • 1
  1. 1.Department of AnatomyMcGill UniversityMontrealCanada

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