H-2 Antigens pp 501-515 | Cite as

A Role for Ia Antigens in B Cell Activation: Studies with Normal B Cells and A B Cell Lymphoma

  • Arthur R. Baluyut
  • V. Udhyakumar
  • J. Morris
  • Bondada Subbarao
Part of the NATO ASI Series book series (NSSA, volume 144)


Monoclonal anti-Ia antibodies enhanced anti-μ induced proliferation of murine B lymphocytes. Anti-Ia induced augmentation of B cell proliferation was allele specific and did not require participation by T cells and adherent cells. The effects of anti-Ia antibodies on B cell activation are neither due to induction of interleukin-1 secretion in the cultures nor due to interaction with the Fc receptors and can be demonstrated under serum-free culture conditions. Monoclonal antibodies against both IA and IE region encoded Ia molecules were able to synergize with anti-μ in inducing B cell proliferation. Antibodies to both IA and IE coded antigens induced IgM secretion from the B lymphoma cell lines BKS3 and BKL. The anti-Ia antibodies did not affect the proliferation of the B lymphoma cells. These results suggest that the interaction of B cell surface Ia with the anti-Ia antibodies results in an activation signal and that the B cell surface Ia antigens may function as signal transducer molecules.


Cell Lymphoma Spleen Cell Proliferative Response Limulus Amebocyte Lysate Assay Monoelonal Antibody 
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  1. Andersson, J., Schreier, M.H. and Melchers, F. T-cell dependent B-cell stimulation is H-2 restricted and antigen dependent only at the resting B-cell level. Proc. Natl. Acad. Sci. USA. 77: 1612–1616, 1980.PubMedCrossRefGoogle Scholar
  2. Andersson, J. and Melchers, F. T cell-dependent activation of resting B cells: Requirements for both nonspecific unrestricted and antigen-specific Ia-restricted soluble factors. Proc. Natl. Acad. Sci. USA. 78: 2497, 1981.CrossRefGoogle Scholar
  3. Bishop, G.A. Fnd Haughton, G. Induced differentiation of a transformed clone of Ly-1 B cells by clonal T cells and antigen. Proc. Natl. Acad. Sci. USA 83: 7410–7414, 1986.PubMedCrossRefGoogle Scholar
  4. Cambier, J.C. and Ransom, J.T. Molecular mechanisms of transmembrane signalling in B lymphocytes. Ann. Rev. Immunol. 5: 175–199, 1987.CrossRefGoogle Scholar
  5. Cambier, J.C., Justement, L.B., Newell, M.K., Chen, Z.Z., Harris, L.K., Sandoval, V.M., Klemsz, M.F., and Ransom, J.T. Transmembrane signals and intracellular “second messengers” in the regulation of quiescent B lymphocyte activation. Immunol. Rev. 95: 37–85, 1987.PubMedCrossRefGoogle Scholar
  6. Chen. Z.Z., McGuire, J.C., Leach, K.L. and Cambier, J.C. Transmembrane signaling through B cell MHC class II molecules: Anti-Ia antibodies induce protein kinase C translocation to the nuclear fraction. J. Immunol. 138: 2345–2352, 1987.PubMedGoogle Scholar
  7. Chestnut, R.W. and Grey, H.M. Studies on the capacity of B cells to serve as antigen-presenting cells. J. Immunol. 126: 1075–1079, 1981.Google Scholar
  8. Clement, L.T., Tedder, T.F. and Gartland, G.L. Antibodies reactive with class II antigens encoded for by the major histocompatibility complex inhibit human B cell activation. J. Immunol. 136: 2375–2381, 1986.PubMedGoogle Scholar
  9. Corbel, C., and Melchers, F. The synergism of accessory cells and of soluble -factors derived from them in the activation of B cells to proliferation. Immunol. Rev. 78: 51–75, 1984.PubMedCrossRefGoogle Scholar
  10. Finnegan, A., Needleman, B. and Hodes, R.J. Activation of B cells by autoreactive T cells: Cloned autoreactive T cells activate B cells by two distinct pathways. J. Immunol. 133: 78–85, 1984.PubMedGoogle Scholar
  11. Forsgren„ S., Martinez, C. and Coutinho, A. The role of I-A/E molecules in B lymphocyte activation II. Mechanism of inhibition of the responses to lipopolysaccharide by anti-I-A/E antibodies. Scand. J. Immunol. 25: 225–234, 1987.CrossRefGoogle Scholar
  12. Forsgren, S., Pobor, G., Coutinho, A., and Pierres, M. The role of I-A/E molecules in B lymphocyte activation: Inhibition of lipopolysaccharideinduced responses by monoclonal antibodies. J. Immunol. 133: 2104–2110, 1984.PubMedGoogle Scholar
  13. Haughton, G., Arnold, L.W., Bi shop, G.A., and Mercol i no, T.J. The CH series of murine B cell lymphomas: Neoplastic analogues of Ly-1+ normal B cells. Immunol. Rev. 93: 35–52, 1986.PubMedCrossRefGoogle Scholar
  14. Howard, M., Mizel, S.B., Lachman, L., Assel,J., Johnson, B. and Paul, W.E. Role of interleukin-1 in anti-immunoglobulin induced B cell proliferation. J. Exp. Med. 157: 1529–1543, 1983.PubMedCrossRefGoogle Scholar
  15. Howard, M., Nakanishi, K. and Paul, W.E. B cell growth and differentiation factors. Immunol. Rev. 78: 185–210, 1984.Google Scholar
  16. Julius, M.H. Reciprocity in lymphocyte interactions. Immunol. Rev. 95: 177–194, 1987.PubMedCrossRefGoogle Scholar
  17. Julius, M.H., Heusser, C.H. and Hartmann, K.U. Induction of resting B cells to DNA synthesis by soluble monoclonal anti-immunoglobulin. Eur. J. Immunol. 14: 753–757, 1984.PubMedCrossRefGoogle Scholar
  18. Klaus, G.G.B. Unravelling the control of B cells. Nature 324: 16–17, 1986.PubMedCrossRefGoogle Scholar
  19. Kung, J.T., Sharrow, S.O, Sieckmann, D.G., Lieberman, R., and Paul, W.E.. A mouse IgM allotypic determinant (Igh 6.5) recognized by a monoclonal rat antibody. J. Immunol. 127: 873–876, 1981.PubMedGoogle Scholar
  20. Ledbetter, J.A. and Herzenberg, LA. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol. Rev. 47: 63–90, 1979.PubMedCrossRefGoogle Scholar
  21. Locascio, N.J., Haughton, G., Arnold, L.W., and Corley, R.G. Role of cell surface immunoglobulin in B-lymphocyte activation. Proc. Natl. Acad. Sci. USA. 81: 2466–2469, 1984.PubMedCrossRefGoogle Scholar
  22. Marrack, P., Kappler, J.W., Skidmore, B., and White, J. Antigen-induced, H-2 restricted, interleukin-2 producing T cell hybridomas. J. Exp. Med. 153: 1198–1214, 1981.PubMedCentralPubMedCrossRefGoogle Scholar
  23. Marshak-Rothstein, A., Fink, P., Gridley, T., Raulet, D.G., Bevan, M.J., and Gefter, M.L. Properties and application of monoclonal antibodies directed against determinants of the Thy-1 locus. J. Immunol. 122: 2491–2497, 1979.PubMedGoogle Scholar
  24. Melchers, F. and Lernhardt, W. Three restriction points in the cell cycle of activated murine B lymphocytes. Proc. Natl. Acad. Sci. USA 82: 7681–7685, 1985.PubMedCrossRefGoogle Scholar
  25. MiL, S.B., Oppenheim, J.J., and Rosenstreich, P.L. Characterization of lymphocyte activating factor (LAF) produced by the macrophage cell line, P388D1. J. Immunol. 120: 1497–1503, 1978.Google Scholar
  26. Mond, J.J., Seghal, E., Kung, J., and Finkelman, F.D. Increased expression of I-region associated antigens (IA) on B cells after cross-linking of surface Ig. J. Immunol. 127: 881–888, 1981.PubMedGoogle Scholar
  27. Mosier, D.E. Primary in vitro antibody responses by purified murine B lymphocytes in serum-free defined medium. J. Immunol. 127: 1490–1493, 1981.PubMedGoogle Scholar
  28. Nagarkatti, P.S., Snow, E.C., and Kaplan, A.M. Characterization and function of autoreactive T lymphocyte clones isolated from normal unprimed mice. Cell Immunol. 94: 32–48, 1985.PubMedCrossRefGoogle Scholar
  29. Niederhuber, J.E., Frelinger, J.A., Dugan, E., Coutinho, A., and Shreffler, D.C. Effects of anti-Ia serum on mitogenic responses: Inhibiton of the proliferative response to B cell mitogen. J. Immunol. 115: 1672–1676, 1975.PubMedGoogle Scholar
  30. Noelle, R., Krammer, P.H., O’Hara, J., Uhr, J.W., and Vitteta.E.S. Increased expression of Ia antigens on resting B cells: An additional role for B-cell growth factor. Proc. Natl. Acad. Sci. USA. 81: 6149–6153, 1984.PubMedCrossRefGoogle Scholar
  31. Oi, V.T., Jones, P.P., Goding, J.W., Herzenberg, L.A., and Herzenberg, L.A. Properties of monoclonal antibodies to mouse Ig allotypes and Ia antigens. Current Topics in Microbiol. and Immunol. 81: 115–129, 1978.Google Scholar
  32. Ozato, K., Mayer, N., and Sachs, D.H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J. Immunol. 124: 533–540, 1980.PubMedGoogle Scholar
  33. Palacios, R. Monoclonal antibodies against human la antigens stimulate monocytes to secrete interleukin-1. Proc. Natl. Acad. Sci. USA. 82: 6652–6656, 1985.PubMedCrossRefGoogle Scholar
  34. Palacios, R., Martinez-Maza, D. and Guy, K. Monoclonal antibodies against HLA-DR antigens replace T helper cells in activation of B lymphocytes. Proc. Natl. Acad. Sci. USA 80: 3456–3460, 1983.PubMedCrossRefGoogle Scholar
  35. Phyllips, N.E. and Parker, D.C. Crosslinking of B lymphocyte Fc-y receptors and membrane immunoglobulin inhibits anti-immunoglobulin-induced bl astogenesi s. J. Immunol. 132: 627–632, 1982.Google Scholar
  36. Pierres, M., Devaux, C., Dosseto, M., and Marchetto, S. Clonal analysis of B- and T-cell respones to la antigents. 1. Topology of epitope regions on I-A1` and I-Er’ molecules analyzied with 35 monoclonal antibodies. Immunogenetics 14: 481–495, 1981.PubMedCrossRefGoogle Scholar
  37. Pierres, M., Kourilsky F.M. Rebouah, J.P., Dosseto, M., and Carillof, D. Distinct epitopes on I gene products identified by monoclonal antibodies. Eur. J. Immunol. 10: 950–957, 1980.PubMedCrossRefGoogle Scholar
  38. Pike, B.L. and Nossal, G.J.V. Interleukin-1 can act as a B cell growth and differentiation factor. Proc. Natl. Acad. Sci. USA. 82: 8153–8157, 1985.PubMedCrossRefGoogle Scholar
  39. Pobor, G., Pettersson, S., Bundeira, A., Martinez, A.C., and Coutinho, A. B lymphocyte activation upon exclusive recognition of major histocompatibility antigens by T helper cells. Eur. J. Immunol. 14: 222–227, 1984.PubMedCrossRefGoogle Scholar
  40. Sprent, J. Role of H-2 gene products in the function of T-helper cells from normal and chimeric mice in vivo. Immunol. Rev. 42: 108–137, 1978.PubMedCrossRefGoogle Scholar
  41. Subbarao, B. and Mosier, D.E. Role of B cell differentation antigens in the activation of B lymphocytes. Immunol. Rev. 69: 81–97, 1982.PubMedCrossRefGoogle Scholar
  42. Subbarao, B. and Mosier, D.E. Induction of B lymphocyte proliferation by monoclonal anti-Lyb2 antibody. J. Immunol. 130: 2033–2037, 1983.PubMedGoogle Scholar
  43. Unkeless, J. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J. Exp. Med. 150: 580–596, 1979.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Arthur R. Baluyut
    • 1
  • V. Udhyakumar
    • 1
  • J. Morris
    • 1
  • Bondada Subbarao
    • 1
  1. 1.Department of Microbiology and Immunology Sanders-Brown Center on AgingUniversity of KentuckyLexingtonUSA

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