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Mechanisms of Lymphocyte Activation and Immune Regulation V pp 35–43Cite as

Accessory Molecules that Influence Signaling Through B Lymphocyte Antigen Receptors

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 365))

Abstract

The B lymphocyte antigen receptor complex, commonly called the B cell receptor (BCR) complex, consists of surface immunoglobulin (sIg) and heterodimers of the Igα (CD79a, mb1) and Igβ (CD79b, B29) phosphoglycoproteins. Recent reviews detail pertinent findings on the BCR complex.1 The structure of the BCR complex and some cell-surface molecules that influence signaling via the BCR are shown in Figure 1. The clonotypic Ig receptor has only a very short cytoplasmic tail and therefore must rely on the invariant members of the BCR complex to transmit signals to the cytosol after receptor crosslinking. Igα/Igβ associate with sIgM and sIgD and are both necessary and sufficient for the expression of sIg. This heterodimer is analogous to the TCR CD3ε/δ or CD3ε/γ heterodimers,2 which, like Igα/Igβ, (1) contain subunits with a single extracellular Ig-like domain; (2) are phosphorylated on tyrosine (CD3ε and CD3ζ) after crosslinking of antigen receptors; and (3) contain within their cytoplasmic tail a single antigen receptor homology 1 (ARH1) motif, D/E-X7-D/E-X2-Y-X2-L-X7-Y-X2-L/I (X = any amino acid). Regions within the transmembrane domain of sIgM are required for the release of [Ca2+]i or internalization of bound antigen.3 Mutations within the transmembrane domain of sIgM that inhibit the activation of new protein tyrosine phosphorylation (PTP) and release of [Ca2+]i also uncouple sIgM from Igα/Igβ.4 However, even though such a mutant sIgM does not associate with Igα/Igβ, when crosslinked it still induces some new PTP.4 Both Sanchez et al.4 and Kim et al.5 reported that surface chimeric fusion proteins expressing the cytoplasmic tails of Igα vs. Igβ differ in their ability to transmit signals: the Igα but not the Igβ tail can induce new PTP, results consistent with studies suggesting that Igα and not Igβ strongly associates with the protein tyrosine kinase (PTK) p53/56Lyn (Lyn).6 Matsuuchi et al.7 found that sIgM expression could be reconstituted in a pituitary cell line with Igα/Igβ coexpression, but that Igα/Igβ were not sufficient to reconstitute a complete signal through sIgM. Thus, IgM interaction with Igα/Igβ is critical for signaling but other factors may also be required.

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Authors and Affiliations

  1. Department of Microbiology, University of Washington Medical Center SC-42, Seattle, WA, 98195, USA

    Edward A. Clark, Ingolf Berberich, Stephen J. Klaus, Che-Leung Law & Svetlana P. Sidorenko

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  1. Edward A. Clark
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  2. Ingolf Berberich
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  3. Stephen J. Klaus
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  4. Che-Leung Law
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  5. Svetlana P. Sidorenko
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Editors and Affiliations

  1. Department of Medicine, University of California, Irvine, CA, 92717-4069, USA

    Sudhir Gupta

  2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892-0001, USA

    William E. Paul

  3. Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143-0552, USA

    Anthony DeFranco

  4. Department of Immunology, University of Washington, Seattle, WA, 98915, USA

    Roger M. Perlmutter

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Clark, E.A., Berberich, I., Klaus, S.J., Law, CL., Sidorenko, S.P. (1994). Accessory Molecules that Influence Signaling Through B Lymphocyte Antigen Receptors. In: Gupta, S., Paul, W.E., DeFranco, A., Perlmutter, R.M. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation V. Advances in Experimental Medicine and Biology, vol 365. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0987-9_4

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