Abstract
A panel of monoclonal antibodies and ligands that bind to the CR1 or CR2 complement receptors of B cells has been used to investigate the role of these membrane molecules in regulating B-cell proliferation and differentiation. When CR2 was modulated from the surface of B cells by treatment with the HB-5 antibody and a secondary goat anti-mouse immunoglobulin antibody, Epstein-Barr virus-induced polyclonal B-cell proliferation and immunoglobulin production were inhibited by 83 and 90%, respectively. In contrast, modulation of other cell surface molecules, HB-2, B1, and the C3b receptor (CR1), or pretreatment of B cells with C3d,g (a CR2 ligand) or HB-5 antibody, alone minimally inhibited these responses. Neither the HB-5 antibody C3d,g, nor a monoclonal antibody (YZ-1) reactive with CR1 induced resting B cells to proliferate, nor did they alter anti-μ antibody-induced proliferation. Similarly, treatment with C3d,g or with the HB-5 or YZ-1 antibodies did not induce B cells to secrete immunoglobulin or affect pokeweed mitogen-induced plasma-cell formation. Whereas CR2 appears to be the functionally relevant receptor for Epstein-Barr virus on B cells, the effects of ligand interactions with CR1 and CR2 on normal B-cell proliferation or differentiation remain unidentified.
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Ross GR, Polley MJ, Rabellino EM, Grey HM: Two different complement receptors on human lymphocytes. One specific for C3b and one specific for C3b inactivator-cleaved C3b. J Exp Med 138:798, 1973
Eden A, Miller GW, Nussenzweig V: Human lymphocytes bear membrane receptors for C3b and C3d. J Clin Invest 52:3239, 1973
Weis JJ, Tedder TF, Fearon DT: Identification of a 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes. Proc Natl Acad Sci USA 81:881, 1984
Iida K, Nadler L, Nussenzweig V: Identification of the membrane receptor for the complement fragment C3d by means of a monoclonal antibody. J Exp Med 158:1021, 1983
Tedder TF, Clement LT, Cooper MD: Expression of C3d receptors during human B cell differentiation: Immunofluorescence analysis with the HB-5 monoclonal antibody. J Immunol 133:678, 1984
Nadler LM, Stashenko P, Hardy R, van Agthoven A, Terhorst C, Schlossman SF: Characterization of a human B cell-specific antigen (B2) distinct from B1. J Immunol 126:1941, 1981
Fearon DT: Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med 152:20, 1980
Tedder TF, Fearon DT, Gartland GL, Cooper MD: Expression of C3b receptors on human B cells and myelomonocytic cells but not natural killer cells. J Immunol 130:1688, 1983
Wilson JG, Tedder TF, Fearon DT: Characterization of human T lymphocytes that express the C3b receptor. J Immunol 131:684, 1983
Jondal M, Klein G, Oldstone MBA, Bokish V, Yefenof E: Surface markers on human B and T lymphocytes. VIII. Association between complement and Epstein-Barr virus receptors on human lymphoid cells. Scand J Immunol 5:401, 1976
Einhorn L, Steinitz M, Yefenof E, Ernberg I, Bakacs T, Klein G: Epstein-Barr virus (EBV) receptors, complement receptors, and EBV infectibility of different lymphocyte fractions of human peripheral blood. II Epstein-Barr virus studies. Cell Immunol 35:43, 1978
Yefenof E, Klein G, Kvarnung K: Relationships between complement activation, complement binding, and EBV absorption by human hematopoietic cell lines. Cell Immunol 31:225, 1977
Magrath I, Freeman C, Santaella M, Gadek J, Frank M, Spiegel R, Novikovs L: Induction of complement receptor expression in cell lines derived from human undifferentiated lymphomas. II. Characterization of the induced complement receptors and demonstration of the simultaneous induction of EBV receptor. J Immunol 127:1039, 1981
Yefenof E, Klein G, Jondal M, Oldstone MBA: Surface markers on human B- and T-lymphocytes. IX. Two-color immunofluorescence studies on the association between EBV receptors and complement receptors on the surface of lymphoid cell lines. Int J Cancer 17:693, 1976
Yefenof E, Klein G: Membrane receptor stripping confirms the association between EBV receptors and complement receptors on the surface of human B lymphoma lines. Int J Cancer 20:347, 1977
Jonsson V, Wells A, Klein G: Receptors for the complement C3d component and the Epstein-Barr virus are quantitatively coexpressed on a series of B-cell lines and their derived somatic cell hybrids. Cell Immunol 72:263, 1982
Simmons JG, Hutt-Fletcher LM, Fowler E, Feighny RJ: Studies of the Epstein-Barr virus receptor found on Raji cells. I. Extraction of receptor and preparation of anti-receptor antibodies. J Immunol 130:1303, 1983
Fingeroth JD, Weis JJ, Tedder TF, Strominger JL, Biro PA, Fearon DT: Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor (CR2). Proc Natl Acad Sci USA 81:4510, 1984
Frade R, Barel M, Ehlin-Henriksson B, Klein G: gp140, the C3d receptor of human B lymphocytes, is also the Epstein-Barr virus receptor. Proc Natl Acad Sci USA 82:1490, 1985
Daha MR, Bloem AC, Bast EJ, Ballieux RE: Immunoglobulin production by human peripheral lymphocytes induced by anti-C3 receptor antibodies. Immunobiology 164:227, 1983
Frade R, Crevon MC, Barel M, Vasquez A, Krikorian L, Charriaut C, Galanaud P: Enhancement of human B cell proliferation by an antibody to the C3d receptor, the gp140 molecule. Eur J Immunol 15:73, 1985
Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 21 (Suppl 97):77, 1968
Pellegrino MA, Ferrone S, Dierich MP, Reisfield RA: Enhancement of sheep red blood cell-human lymphocyte rosette formation by the sulfhydryl compound 2-aminoethylisothiouronium bromide. Clin Immunol Immunopathol 7:804, 1975
Clement LT, Dagg MK, Gartland GL: Small, resting B cells can be induced to proliferate by direct signals from activated helper T cells. J Immunol 132:740, 1984
Changelian PS, Jack RM, Collins LA, Fearon DT: PMA induces the ligand-independent internalization of CR1 on human neutrophils. J Immunol 134:1851, 1985
Landay A, Gartland GL, Abo T, Cooper MD: Enumeration of human lymphocyte subpopulations by immunofluorescence: A comparative study using automated flow microfluorometry and fluorescence microscopy. J Immunol Methods 58:337, 1983
Tedder TF, Clement LT, Cooper MD: Discontinuous expression of a membrane antigen (HB-7) during B lymphocyte differentiation. Tissue Antigens 24:140, 1984
Gathings WE, Lawton AR, Cooper MD: Immunofluorescent studies of the development of pre-B cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol 7:804, 1977
Vik DP, Fearon DT: Neutrophils express a receptor for iC3b, C3dg, and C3d that is distinct from CR1, CR2, and CR3. J Immunol 134:2571, 1985
Miller G, Lipman M: Comparison of the yield of infectious virus from clones of human and simian lymphoblastoid lines transformed by Epstein-Barr virus. J Exp Med 138:1398, 1983
Phillips NE, Parker DC: Cross-linking of B lymphocyte Fc receptors and membrane immunoglobulin inhibits anti-immunoglobulin-induced blastogenesis. J Immunol 132:627, 1984
Maruyama S, Kubagawa H, Cooper MD: Activation of human B cells and inhibition of their terminal differentiation by monoclonal anti-μ antibodies. J Immunol (in press)
Clement LT, Dagg MK, Lehmeyer JE, Kiyotaki M: Two phenotypically distinct suppressor T cell subpopulations inhibit the induction of B cell differentiation by phytohemagglutinin. J Immunol 131:1214, 1983
Bird AG, Britton S: A New approach to the study of human B lymphocyte function using an indirect plaque assay and a direct B cell activator. Immunol Rev 45:41, 1979
Sitia R, Rabellino EM, Sockell M, Hammerling U: A spatial association between membrane IgD and the receptor for C3b (CR1) at the cell surface of murine B lymphocytes. J Immunol 126:107, 1981
Lobo PI, Burge JJ:In vitro studies on the immune regulatory role of complement receptors (C3) present on human B lymphocytes. Eur J Immunol 12:682, 1982
Tsokos GC, Berger M, Balow JE: Modulation of human B cell immunoglobulin secretion by the C3b component of complement. J Immunol 132:622, 1984
Rosen A, Gergely P, Jondal M, Klein G, Britton S: Polyclonal Ig production after Epstein-Barr virus infection of human lymphocytesin vitro. Nature 267:52, 1977
Thorley-Lawson DA, Strominger JL: Reversible inhibition by phosphonoacetic acid of human B lymphocyte transformation by Epstein-Barr virus. Virology 86:423, 1978
Fu SM, Hurley JN, McCune JM, Kunkel HG, Good RA: Pre-B cells and other possible precursor lymphoid cell lines derived from patients with X-linked agammaglobulinemia. J Exp Med 152:1519, 1980
Thorley-Lawson DA, Chess L, Strominger JL: Suppression ofin vitro Epstein-Barr virus infection. A new role for adult human T lymphocytes. J Exp Med 146:495, 1977
Rao PE, Wright SD, Westberg EF, Goldstein G: OKB7, a monoclonal antibody that reacts at or near the C3d binding site of human CR2. Cell Immunol 93:549, 1985
Schreiber AB, Libermann TA, Lax I, Yarden Y, Schlessinger J: Biological role of epidermal growth factor-receptor clustering. Investigation with monoclonal anti-receptor antibodies. J Biol Chem 258:846, 1983
Meuer SC, Hussey RE, Cantrell DA, Hodgdon JC, Schlossman SF, Smith KA, Reinherz EL: Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci 81:1509, 1984
Nemerow GR, Wolfert R, McNaughton M, Cooper NR: Identification of the Epstein-Barr virus receptor and its relationship to complement C3d receptor (CR2). Fed Proc 44:988, 1985 (abstr)
Wilson BS, Platt JL, Kay NE: Stimulation of B cell DNA synthesis by monoclonal antibodies to the CR2 (C3d) complement fragment receptor. Fed Proc 44:1876, 1985 (abstr)
Klaus GGB, Humphrey JH: The generation of memory cells. I. The role of C3 in the generation of B memory cells. Immunology 33:34, 1977
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Tedder, T.F., Weis, J.J., Clement, L.T. et al. The role of receptors for complement in the induction of polyclonal B-cell proliferation and differentiation. J Clin Immunol 6, 65–73 (1986). https://doi.org/10.1007/BF00915366
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DOI: https://doi.org/10.1007/BF00915366