Signaling and Internalisation Function of the B Cell Antigen Receptor Complex

  • Heinrich Flaswinkel
  • Peter Weiser
  • Kwang-Myong Kim
  • Michael Reth
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 365)


The mouse B-cell antigen receptor (BCR) is a multi-component transmembrane protein complex. This complex is comprised of the membrane-bound immunoglobulin (mIg) and the disulfide-linked Ig-α and Ig-β heterodimer which is non-covalently associated with all classes of mIg molecules,1 (for review see references 2–4). Ig-α and Ig-β are glycoproteins of Mr 34000 and Mr 39000,5,6,1 which are encoded by the B-cell specific genes mb-17 and B29,8 respectively. Both proteins carry extracellularly a glycosylated Ig-like domain, a single transmembrane region of 22 amino acids, and a cytoplasmic portion of either 61 or 48 amino acids. The transmembrane and the cytoplasmic part of Ig-α and Ig-β is strongly conserved between the mouse and the human proteins.9–13


Cytoplasmic Tail Antigen Receptor Bovine Leukaemia Virus Cell Antigen Receptor Substrate Phosphorylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A.R. Venkitaraman, G.T. Williams, P. Dariavach, and M.S. Neuberger, The B-cell antigen receptor of the five immunoglobulin classes, Nature 352:777 (1991).PubMedCrossRefGoogle Scholar
  2. 2.
    M. Reth, Antigen receptors on B lymphocytes, Annual Rev Immunol 10:97 (1992).CrossRefGoogle Scholar
  3. 3.
    N. Sakaguchi, T. Matsuo, J. Nomura, K. Kuwahare, H. Igarashi, and S. Inui, Immunoglobulin receptor-associated molecules, Adv Immunol 54:337 (1993).PubMedCrossRefGoogle Scholar
  4. 4.
    A.L. DeFranco, Structure and function of the B cell antigen receptor, Annual Rev Cell Biol 9:377–410 (1993).CrossRefGoogle Scholar
  5. 5.
    D. Hombach, F. Lottspeich, and M. Reth, Identification of the genes encoding the IgM-α and Ig-β components of the IgM antigen receptor complex by aminoterminal sequencing, Eur J Immunol 20:2795 (1990).PubMedCrossRefGoogle Scholar
  6. 6.
    K.S. Campbell and J.C. Cambier, B lymphocyte antigen receptors (mIg) are non-covalently associated with a disulfide linked inducible phosphorylated glycoprotein complex, EMBO J 9:441 (1990).PubMedGoogle Scholar
  7. 7.
    N. Sakaguchi, S. Kashiwamura, M. Kimoto, P. Thalmann, and F. Melchers, B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties, EMBO J 7:3457 (1988).PubMedGoogle Scholar
  8. 8.
    G.G. Hermanson, D. Eisenberg, P.W. Kincade, and R. Wall, B29: a member of the immunoglobulin gene superfamily exclusively expressed on B-lineage cells, Proc Natl Acad Sci USA 85:6890 (1988).PubMedCrossRefGoogle Scholar
  9. 9.
    L.M. Yu and T.W. Chang, Human mb-1 gene: complete cDNA sequence and its expression in B cells bearing membrane Ig of various isotypes, J Immunol 148:633 (1992).PubMedGoogle Scholar
  10. 10.
    H.J. Ha, H. Kubagawa, and P.D. Burrows, Molecular cloning and expression pattern of a human gene homologous to the murine mb-1 gene, J Immunol 148:1526 (1992).PubMedGoogle Scholar
  11. 11.
    H. Flaswinkel and M. Reth, Molecular cloning of the Ig-α subunit of the human B-cell antigen receptor complex, Immunogenetics 36:266 (1992).PubMedCrossRefGoogle Scholar
  12. 12.
    B. Müller, L. Cooper, and C. Terhorst, Cloning and sequencing of the cDNA encoding the human homologue of the murine immunoglobulin-associated protein B29, Eur J Immunol 222:1621 (1992).CrossRefGoogle Scholar
  13. 13.
    S. Hashimoto, P.K. Gregersen, and N. Chiorazzi, The human Ig-β cDNA sequence, a homologue of murine B29, is identical in B cell and plasma cell lines producing all the human Ig isotypes, J Immunol 150:491 (1993).PubMedGoogle Scholar
  14. 14.
    M. Reth, Antigen receptor tail clue, Nature 338:383 (1989).PubMedCrossRefGoogle Scholar
  15. 15.
    L.E. Samelson and R.D. Klausner, Tyrosine kinases and tyrosine-based activation motifs, J Biol Chem 267:24913 (1992).PubMedGoogle Scholar
  16. 16.
    J.C. Cambier, Signal transduction by T-and B-cell antigen receptors: converging structures and concepts, Curr Opin Immunol 4:257 (1992).PubMedCrossRefGoogle Scholar
  17. 17.
    F. Letourneur and R.D. Klausner, T-cell and basophil activation through the cytoplasmic tail of T-cell-receptor zeta family proteins, Proc Natl Acad Sci USA 88:8905 (1991).PubMedCrossRefGoogle Scholar
  18. 18.
    A.-M.K. Wegener, F. Letourneur, A. Hoeveler, T. Brocker, F. Luton, and B. Malissen, The T cell receptor/CD3 complex is composed of at least two autonomous transduction molecules, Cell 68:83 (1992).PubMedCrossRefGoogle Scholar
  19. 19.
    C. Romeo, M. Amiot, and B. Seed, Sequence requirements for the induction of cytolysis by the T cell antigen/Fc receptor ζ chain, Cell 68:889 (1992).PubMedCrossRefGoogle Scholar
  20. 20.
    B. A. Irving, A.C. Chan, and A. Weiss, Functional characterization of a signaling transducing motif present in the T cell antigen receptor ζ chain, J Exp Med 177:1093 (1993).PubMedCrossRefGoogle Scholar
  21. 21.
    G. Alber, K.M. Kim, P. Weiser, C. Riesterer, R. Carsetti, and M. Reth, Molecular mimicry of the antigen receptor signaling motif by transmembrane proteins of the Epstein-Barr virus and the bovine leukaemia virus, Current Biology 3:333 (1993).PubMedCrossRefGoogle Scholar
  22. 22.
    P. Beaufils, D. Choquat, R.Z. Mamoun and B. Malissen, The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and the Epstein-Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events, EMBO J 12:5105 (1993).PubMedGoogle Scholar
  23. 23.
    Y. Yamanashi, T. Kakiuchi, J. Mizuguchi, T. Yamamoto, and K. Toyoshima, Association of B cell antigen receptor with protein tyrosine kinase Lyn, Science 251:192 (1991).PubMedCrossRefGoogle Scholar
  24. 24.
    A.L. Burkhardt, M. Brunswick, J.B. Bolen, and J. J. Mond, Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases, Proc Natl Acad Sci USA 88:7410 (1991).PubMedCrossRefGoogle Scholar
  25. 25.
    J. Lin and L.B. Justement, The MB-1/B29 heterodimer couples the B cell antigen receptor to multiple src family protein tyrosine kinases, J Immunol 149: 1548 (1992).PubMedGoogle Scholar
  26. 26.
    M.A. Campbell and B.M. Sefton, Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases, Mol Cell Biol 12:2315 (1992).PubMedGoogle Scholar
  27. 27.
    J.E. Hutchcroft, M.L. Harrison, and R.L. Geahlen, Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor, J Biol Chem 267:8613 (1992).PubMedGoogle Scholar
  28. 28.
    T. Taniguchi, T. Kobayashi, T. Kondo, J. Takahashi, K. Nakamura, H. Suzuki, J. Nagai, T. Yamada, S. Nakamura, and H. Yamamura, Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis, J Biol Chem 266:15790 (1991).PubMedGoogle Scholar
  29. 29.
    D.A. Law, V.W.F. Chan, S.K. Datta, and A.L. DeFranco, B-cell antigen receptor motifs have redundant signalling capabilities and bind the tyrosine kinases PTK72, Lyn and Fyn, Current Biology 3:645 (1993).PubMedCrossRefGoogle Scholar
  30. 30.
    K.M. Kim, G. Alber, P. Weiser, and M. Reth, Differential signaling through the Ig-α and Ig-β components of the B cell antigen receptor, Eur J Immunol 23:911 (1993).PubMedCrossRefGoogle Scholar
  31. 31.
    F. Letourneur and R.D. Klausner, Activation of T cells by a tyrosine kinase activation domain in the cytoplasmic tail of CD3e, Science 255:79 (1992).PubMedCrossRefGoogle Scholar
  32. 32.
    M. Sanchez, Z. Misulovin, A.L. Burkhardt, S. Mahajan, T. Costa, R. Franke, J.B. Bolen, and M. Nussenzweig, Signal transduction by immunoglobulin is mediated through Ig-α and Ig-β, J Exp Med 178:1049 (1993).PubMedCrossRefGoogle Scholar
  33. 33.
    J. Hombach, F. Sablitzky, K. Rajewsky, and M. Reth, Transfected plasmacytoma cells do not transport the membrane form of IgM to the cell surface, J Exp Med 167:652 (1988).PubMedCrossRefGoogle Scholar
  34. 34.
    J. Hombach, T. Tsubata, L. Leclercq, H. Stappert, and M. Reth, Molecular components of the B cell antigen receptor complex of the IgM class, Nature 343:760 (1990).PubMedCrossRefGoogle Scholar
  35. 35.
    K.M. Kim, G. Alber, P. Weiser, and M. Reth, The B-cell antigen receptor complex, Immunol Reviews 132:125 (1993).CrossRefGoogle Scholar
  36. 36.
    J. Wienands and M. Reth, Glycosyl-phosphatidylinositol linkage as a mechanism for cell-surface expression of immunoglobulin D, Nature 356:246 (1992).PubMedCrossRefGoogle Scholar
  37. 37.
    J.C. Antoine, S. Avrameas, N.K. Gonatas, A. Stieber, and J.O. Gonatas, Plasma membrane and internalized immunoglobulins of lymph node cells studied with conjugates of antibody or its Fab fragments with horseradish peroxidase, J Cell Biol 63:12 (1974).PubMedCrossRefGoogle Scholar
  38. 38.
    E.R. Unanue, Cellular events following binding of antigen to lymphocytes, Amer J Pathol 77:2 (1974).Google Scholar
  39. 39.
    A. Lanzavecchia, Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes, Annual Rev Immunol 8:773 (1990).CrossRefGoogle Scholar
  40. 40.
    S. Amigorena, J. Salamero, J. Davoust, W.H. Fridman, and C. Bonnerot, Tyrosine-containing motif that transduces cell activation signals also determines internalization and antigen presentation via type III receptors for IgG, Nature 358:337 (1992).PubMedCrossRefGoogle Scholar
  41. 41.
    H. Flaswinkel and M. Reth, Dual role of the tyrosine activation motif of the Ig-α protein during signal transduction via the B cell antigen receptor, EMBO J 13:83 (1994).PubMedGoogle Scholar
  42. 42.
    P. Weiser, C. Riesterer, and M. Reth, The internalization of the IgG2a antigen receptor does not require the association with Ig-α and Ig-β but the activation of protein kinases does, Eur J Immunol 24:665 (1994).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Heinrich Flaswinkel
    • 1
  • Peter Weiser
    • 1
  • Kwang-Myong Kim
    • 1
  • Michael Reth
    • 1
  1. 1.Max-Planck-Institut für ImmunbiologieFreiburgGermany

Personalised recommendations