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. 1986 Jun;83(12):4494–4498. doi: 10.1073/pnas.83.12.4494

Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50.

E A Clark, J A Ledbetter
PMCID: PMC323760  PMID: 3487090

Abstract

Two human B-cell differentiation antigens, Bp35 and Bp50, apparently play distinct roles as signal receptors in B-cell activation. Monoclonal antibodies (mAbs) to either Bp35 or Bp50 deliver positive signals to B cells that stimulate their transition through the cell cycle. mAb to Bp35, like anti-immunoglobulin antibodies, functions principally to activate resting B cells to become competent to enter the G1 phase of the cell cycle. In contrast, mAb to Bp50, a 50-kDa polypeptide expressed on all B cells, functions to stimulate activated B cells to traverse the cell cycle. mAb to Bp35, like anti-immunoglobulin antibodies, activates tonsillar B cells and induces low levels of B-cell proliferation. In contrast, anti-Bp50 mAb alone neither activates B cells nor induces B cells to proliferate but, together with anti-Bp35 or anti-immunoglobulin, augments B-cell proliferation. In this respect the action of anti-Bp50 antibody resembles the activity of B-cell growth factor(s) (BCGF). As little as 0.05 microgram of anti-Bp50 per ml is needed to augment proliferation and, like BCGF, anti-Bp50 is effective even when added 12-24 hr after B cells are activated with anti-immunoglobulin or anti-Bp35. Without additional exogenous signals, anti-Bp35 and anti-Bp50 together induce strong proliferation of purified resting B cells. These results suggest that the Bp35 and Bp50 surface molecules function in the regulatory control of B-cell activation and progression through the cell cycle.

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Selected References

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  1. Ambrus J. L., Jr, Fauci A. S. Human B lymphoma cell line producing B cell growth factor. J Clin Invest. 1985 Feb;75(2):732–739. doi: 10.1172/JCI111754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ambrus J. L., Jr, Jurgensen C. H., Brown E. J., Fauci A. S. 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. 1985 Oct 1;162(4):1319–1335. doi: 10.1084/jem.162.4.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clark E. A., Shu G., Ledbetter J. A. Role of the Bp35 cell surface polypeptide in human B-cell activation. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1766–1770. doi: 10.1073/pnas.82.6.1766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Darzynkiewicz Z., Sharpless T., Staiano-Coico L., Melamed M. R. Subcompartments of the G1 phase of cell cycle detected by flow cytometry. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6696–6699. doi: 10.1073/pnas.77.11.6696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DeFranco A. L., Raveche E. S., Paul W. E. Separate control of B lymphocyte early activation and proliferation in response to anti-IgM antibodies. J Immunol. 1985 Jul;135(1):87–94. [PubMed] [Google Scholar]
  6. Defranco A. L., Raveche E. S., Asofsky R., Paul W. E. Frequency of B lymphocytes responsive to anti-immunoglobulin. J Exp Med. 1982 May 1;155(5):1523–1536. doi: 10.1084/jem.155.5.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Frade R., Crevon M. C., Barel M., Vazquez A., Krikorian L., Charriaut C., Galanaud P. Enhancement of human B cell proliferation by an antibody to the C3d receptor, the gp 140 molecule. Eur J Immunol. 1985 Jan;15(1):73–76. doi: 10.1002/eji.1830150114. [DOI] [PubMed] [Google Scholar]
  8. Goding J. W. Conjugation of antibodies with fluorochromes: modifications to the standard methods. J Immunol Methods. 1976;13(3-4):215–226. doi: 10.1016/0022-1759(76)90068-5. [DOI] [PubMed] [Google Scholar]
  9. Golay J. T., Clark E. A., Beverley P. C. The CD20 (Bp35) antigen is involved in activation of B cells from the G0 to the G1 phase of the cell cycle. J Immunol. 1985 Dec;135(6):3795–3801. [PubMed] [Google Scholar]
  10. Howard M., Nakanishi K., Paul W. E. B cell growth and differentiation factors. Immunol Rev. 1984 Apr;78:185–210. doi: 10.1111/j.1600-065x.1984.tb00482.x. [DOI] [PubMed] [Google Scholar]
  11. Howard M., Paul W. E. Regulation of B-cell growth and differentiation by soluble factors. Annu Rev Immunol. 1983;1:307–333. doi: 10.1146/annurev.iy.01.040183.001515. [DOI] [PubMed] [Google Scholar]
  12. Jung L. K., Fu S. M. Selective inhibition of growth factor-dependent human B cell proliferation by monoclonal antibody AB1 to an antigen expressed by activated B cells. J Exp Med. 1984 Dec 1;160(6):1919–1924. doi: 10.1084/jem.160.6.1919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jung L. K., Hara T., Fu S. M. Detection and functional studies of p60-65 (Tac antigen) on activated human B cells. J Exp Med. 1984 Nov 1;160(5):1597–1602. doi: 10.1084/jem.160.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kehrl J. H., Muraguchi A., Butler J. L., Falkoff R. J., Fauci A. S. Human B cell activation, proliferation and differentiation. Immunol Rev. 1984 Apr;78:75–96. doi: 10.1111/j.1600-065x.1984.tb00477.x. [DOI] [PubMed] [Google Scholar]
  15. Kintner C., Sugden B. Identification of antigenic determinants unique to the surfaces of cells transformed by Epstein-Barr virus. Nature. 1981 Dec 3;294(5840):458–460. doi: 10.1038/294458a0. [DOI] [PubMed] [Google Scholar]
  16. Kishimoto T. Factors affecting B-cell growth and differentiation. Annu Rev Immunol. 1985;3:133–157. doi: 10.1146/annurev.iy.03.040185.001025. [DOI] [PubMed] [Google Scholar]
  17. Kronheim S. R., March C. J., Erb S. K., Conlon P. J., Mochizuki D. Y., Hopp T. P. Human interleukin 1. Purification to homogeneity. J Exp Med. 1985 Mar 1;161(3):490–502. doi: 10.1084/jem.161.3.490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  19. Ledbetter J. A., Clark E. A. Surface phenotype and function of tonsillar germinal center and mantle zone B cell subsets. Hum Immunol. 1986 Jan;15(1):30–43. doi: 10.1016/0198-8859(86)90315-0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Ledbetter J. A., Tsu T. T., Clark E. A. Covalent association between human thymus leukemia-like antigens and CD8(Tp32) molecules. J Immunol. 1985 Jun;134(6):4250–4254. [PubMed] [Google Scholar]
  22. Melchers F., Andersson J., Lernhardt W., Schreier M. H. H-2-unrestricted polyclonal maturation without replication of small B cells induced by antigen-activated T cell help factors. Eur J Immunol. 1980 Sep;10(9):679–685. doi: 10.1002/eji.1830100905. [DOI] [PubMed] [Google Scholar]
  23. Melchers F., Erdei A., Schulz T., Dierich M. P. Growth control of activated, synchronized murine B cells by the C3d fragment of human complement. Nature. 1985 Sep 19;317(6034):264–267. doi: 10.1038/317264a0. [DOI] [PubMed] [Google Scholar]
  24. Muraguchi A., Kehrl J. H., Butler J. L., Fauci A. S. Sequential requirements for cell cycle progression of resting human B cells after activation by anti-Ig. J Immunol. 1984 Jan;132(1):176–180. [PubMed] [Google Scholar]
  25. Nemerow G. R., McNaughton M. E., Cooper N. R. Binding of monoclonal antibody to the Epstein Barr virus (EBV)/CR2 receptor induces activation and differentiation of human B lymphocytes. J Immunol. 1985 Nov;135(5):3068–3073. [PubMed] [Google Scholar]
  26. O'Keefe E. J., Pledger W. J. A model of cell cycle control: sequential events regulated by growth factors. Mol Cell Endocrinol. 1983 Aug;31(2-3):167–186. doi: 10.1016/0303-7207(83)90147-8. [DOI] [PubMed] [Google Scholar]
  27. Rabin E. M., Ohara J., Paul W. E. B-cell stimulatory factor 1 activates resting B cells. Proc Natl Acad Sci U S A. 1985 May;82(9):2935–2939. doi: 10.1073/pnas.82.9.2935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Slovin S. F., Frisman D. M., Tsoukas C. D., Royston I., Baird S. M., Wormsley S. B., Carson D. A., Vaughan J. H. Membrane antigen on Epstein--Barr virus-infected human B cells recognized by a monoclonal antibody. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2649–2653. doi: 10.1073/pnas.79.8.2649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stiles C. D., Capone G. T., Scher C. D., Antoniades H. N., Van Wyk J. J., Pledger W. J. Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1279–1283. doi: 10.1073/pnas.76.3.1279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Subbarao B., Mosier D. E. Lyb antigens and their role in B lymphocyte activation. Immunol Rev. 1982;69:81–97. doi: 10.1111/j.1600-065x.1983.tb00450.x. [DOI] [PubMed] [Google Scholar]
  31. Suzuki T., Butler J. L., Cooper M. D. Human B cell responsiveness to B cell growth factor after activation by phorbol ester and monoclonal anti-mu antibody. J Immunol. 1985 Apr;134(4):2470–2476. [PubMed] [Google Scholar]
  32. Swain S. L., Howard M., Kappler J., Marrack P., Watson J., Booth R., Wetzel G. D., Dutton R. W. Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays. J Exp Med. 1983 Sep 1;158(3):822–835. doi: 10.1084/jem.158.3.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thorley-Lawson D. A., Nadler L. M., Bhan A. K., Schooley R. T. BLAST-2 [EBVCS], an early cell surface marker of human B cell activation, is superinduced by Epstein Barr virus. J Immunol. 1985 May;134(5):3007–3012. [PubMed] [Google Scholar]
  34. Wang C. Y., Fu S. M., Kunkel H. G. Isolation and immunological characterization of a major surface glycoprotein (gp54) preferentially expressed on certain human B cells. J Exp Med. 1979 Jun 1;149(6):1424–1437. doi: 10.1084/jem.149.6.1424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wetzel G. D., Swain S. L., Dutton R. W., Kettman J. R. Evidence for two distinct activation states available to B lymphocytes. J Immunol. 1984 Nov;133(5):2327–2332. [PubMed] [Google Scholar]
  36. Zipf T. F., Lauzon G. J., Longenecker B. M. A monoclonal antibody detecting a 39,000 m.w. molecule that is present on B lymphocytes and chronic lymphocytic leukemia cells but is rare on acute lymphocytic leukemia blasts. J Immunol. 1983 Dec;131(6):3064–3072. [PubMed] [Google Scholar]
  37. Zubler R. H., Lowenthal J. W., Erard F., Hashimoto N., Devos R., MacDonald H. R. Activated B cells express receptors for, and proliferate in response to, pure interleukin 2. J Exp Med. 1984 Oct 1;160(4):1170–1183. doi: 10.1084/jem.160.4.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]

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