Regulation of Human B Cell Growth

  • J. L. AmbrusJr.
  • A. S. Fauci
  • K. R. YoungJr.
  • P. McFarland
  • L. Chesky
  • H. Mostowski
  • M. Chandan
  • F. M. Uckun
Conference paper
Part of the Experimental Hematology Today—1988 book series (HEMATOLOGY, volume 1988)


The study of human B cell function involves examination of the events leading to maturation of B cells from B lineage lymphoid progenitor cells as well as the stages of activation, proliferation and differentiation which mature resting B lymphocytes must undergo to become immunoglobulin producing plasma cells [1–3]. In human B cell physiology (as opposed to murine B cell physiology) there appear to be molecules which act only at specific stages to induce either activation, proliferation or differentiation. However, as in murine B cell physiology, there are also molecules which can act at various stages. Antigen or anti-Ig will activate cells while B cell growth factors (BCGFs) [4–8] will induce their proliferation and B cell differentiation factors including interleukin-6 (IL-6) [9–11] will induce their differentiation. IL-2 in high concentrations can induce activation [12], proliferation, and differentiation [13] of human lymphocytes. In the next section, we will discuss some of our work examining the action of BCGFs in the regulation of normal human B cell proliferation.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Dutton RW, Falkoff R, Hurst JA, Hoffman M, Kappler JW, Ketmann JR, Lesley JR (1971) Is there evidence for a non-antibody specific diffusable chemical mediator from the thymus-derived cell in the initiation of the immune response? Prog Immunol 1: 355.Google Scholar
  2. 2.
    Kishimoto T, Miyake T, Nishizawa Y, Watanabe T, Yamamura Y (1975) Triggering mechanism of B lymphocytes. I. Effect of anti-immunoglobulin and enhancing soluble factor on differentiation and proliferation of B cells. J Immunol 1555: 1179.Google Scholar
  3. 3.
    Ambrus JL Jr, Jurgensen CH, Bowen DL, Tomita S, Nakgawa T, Nakagawa N, Goldstein H, Witzel NL, Mostowski HS, Fauci AS (1987) The activation, prolif-eration, and differentiation of human B lymphocytes. Adv Exp Med Biol 213: 163.PubMedCrossRefGoogle Scholar
  4. 4.
    Ambrus JL Jr, Jurgensen CH, Brown EJ, Fauci AS (1985) Purification to homogeneity of a high molecular weight human B cell growth factor, demonstration of specific binding to activated B cells, and development of a monoclonal antibody to the factor. J Exp Med 162: 1319.PubMedCrossRefGoogle Scholar
  5. 5.
    Mehta SR, Conrad D, Sandler R, Morgan J, Montagna R, Maizel AL (1985) Purification of human B cell growth factor. J Immunol 135: 3298.PubMedGoogle Scholar
  6. 6.
    Gordon J, Guy GR (1987) The molecules controling B lymphocytes. Immunol Today 8: 339.CrossRefGoogle Scholar
  7. 7.
    Delfraissay JD, Wallen C, Vazquez A, Dugas B, Dormant J, Galanaud P (1986) B cell hyperactivity in systemic lupus erythematosus: selectively enhanced responsiveness to a high molecular weight B cell growth factor. Eur J Immunol 16: 1251.CrossRefGoogle Scholar
  8. 8.
    Butler JL, Ambrus JL Jr, Fauci AS (1984) Characterization of monoclonal B cell growth factor ( BCGF) produced by a human T-T hybridoma. J Immunol 133: 251.PubMedGoogle Scholar
  9. 9.
    Kishimoto T, Yoshizaki K, Kimoto M, Okada M, Kuritani T, Kikutani H, Shimizu K, Nakagawa T, Nakagawa N, Miki Y, Kishi H, Fukunaga K, Yoshikubo T, and Tag T (1984) B cell growth and differentiation factors and mechanism of B cell activtion. Immunol Rev 78: 97.PubMedCrossRefGoogle Scholar
  10. 10.
    Goldstein H, Volkman DJ, Ambrus JL Jr, Fauci AS (1985) Characterization of a T4+/Leu8+ T cell clone that directly helps B cell Ig production by secreting B cell differention factor. J Immunol 135: 339.PubMedGoogle Scholar
  11. 11.
    Hirano T, Yasukawa K, Horada H, Taga T, Watanabe Y, Matsuda T, et al (1986) Complementary DNA for a novel interleukin (BSF-2) that induces B lymphocyts to produce immunoglobulin. Nature 324: 73–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Le thi Bich Thuy, Lane HC, Fauci AS (1986) Recombinant interleukin-2 induced polyclonal proliferation of in vitro unstimulated human peripheral blood lymphocytes. Cell Immunol 98: 396–410.CrossRefGoogle Scholar
  13. 13.
    Waldmann TA, Goldman CK, Robb RJ, Depper JM, Leonard WJ, Sharrow SO, Bongiovanni KF, Korsmeyer SJ, Greene WG (1984) Expression of interleukin-2 receptors on activated human B cells. J Exp med 160: 14–50.CrossRefGoogle Scholar
  14. 14.
    Greaves MF (1986) Differentiation-linked leukoemogenesis in lymphocytes. Science 234: 697–704.PubMedCrossRefGoogle Scholar
  15. 15.
    Aman P, Ehln-Henriksson B, Klein G (1984) Epstein Barr virus susceptibility of normal human B lymphocyte populations. J Exp Med 157: 208–20.CrossRefGoogle Scholar
  16. 16.
    Muraguchi A, Fauci AS (1982) Proliferative responses of normal human B lymphocytes. Development of an assay for human B cell growth factor ( BCGF ). J Immunol 129: 1104.PubMedGoogle Scholar
  17. 17.
    Ambrus JL Jr, Fauci AS (1985) Human B lymphoma cell line producing B cell growth factor. J Clin Invest 75: 732–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Ambrus JL Jr, Fauci AS (1987) Current studies examining regulation of the human B cell cycle. In: Webb DR, Pierce CW, Cohen S (eds) Molecular basis of lymphokine action, Clifton, New Jersey: Humana Press, 137–148.CrossRefGoogle Scholar
  19. 19.
    Ambrus JL Jr, Jurgensen CH, Brown EJ, McFarland P, Fauci AS (1988) Identification of a receptor for high molecular weight B cell growth factor. J Immunol 141: 660.Google Scholar
  20. 20.
    McFarland P, Ambrus JL Jr, Mostowski H, Fauci AS (1988) Phosphorylation of membrane proteins by activated human B lymphocytes in response to a high molecular weight B cell growth factor. Fed proc 2: A165 (7869).Google Scholar
  21. 21.
    Young KR Jr, Ambrus JL Jr, Chesky L, Chused T, Fauci AS (1988) Heterogeneity of transmembrane signaling pathways triggered by human B lymphocyte activating agents. Fed Proc 2: A1230 (5429).Google Scholar
  22. 22.
    Ambrus JL Jr, Chesky L, McFarland P, Young KR, Jr, Brown EJ, Peters M, Uckun F, Ledbetter J, Fauci AS (1988) High molecular weight B cell growth factor (HMW-BCGF) activtes two distinct pathways of inracellular signaling in SAC-activated human B lymphocytes. Fed Proc 2: A1466 (6796).Google Scholar
  23. 23.
    Ambrus JL Jr, Chused T, Uckun FM, Young KR Jr, Fauci AS (1988) Human B cell growth factors induce calcium fluxes in different subpopulations of activated human B lymphocytes. Manuscript in review.Google Scholar
  24. 24.
    Furth J (1953) Conditoned and autonomous neoplasms: a review. Cancer Res 13: 477–92.PubMedGoogle Scholar
  25. 25.
    Uckun FM, Fauci AS, Heerema NA, Song CW, Mehta SR, Gajl-Peczalska KJ, Chandan M, Ambrus JL Jr (1987) B-cell growth factor receptor expresion and B cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells. Blood 70: 1020–34.PubMedGoogle Scholar
  26. 26.
    Uckun FM, Meyers D, Fauci AS, Ambrus JL Jr (1988) Leukemic B cell precursors constitutively express function receptors for human IL-1. Manuscript in review.Google Scholar
  27. 27.
    Uckun FM, Fauci AS, Chandon M, Ambrus JL Jr (1988) Detection and characterization of human B cell growth factor receptors on leukemic B cells in chronic lymphocytic leukemia. Manuscript in review.Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • J. L. AmbrusJr.
  • A. S. Fauci
  • K. R. YoungJr.
  • P. McFarland
  • L. Chesky
  • H. Mostowski
  • M. Chandan
  • F. M. Uckun

There are no affiliations available

Personalised recommendations