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A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling

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A Correction to this article was published on 26 May 1994

Abstract

THE Fc receptor on B lymphocytes, FcγRIIB (β1 isoform), helps to modulate B-cell activation triggered by the surface immunoglobulin complex1,2. Crosslinking of membrane immunoglobulin by antigen or anti-Ig F(ab′)2 antibody induces a transient increase in cytosolic free Ca2+, a rise in inositol-3-phosphate, activation of protein kinase C, and enhanced protein tyrosine phosphorylation3–5. Crosslinking FcγRIIB with the surface immunoglobulin complex confers a dominant signal that prevents or aborts lymphocyte activation triggered through the ARH-1 motifs of the signal transduction subunits Ig-α and Ig-β. Here we show that FcγRIIB modulates membrane immunoglobulin-induced Ca2+ mobilization by inhibiting Ca2+ influx, without changing the pattern of tyrosine phosphorylation. A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB is both necessary and sufficient for this effect. Tyrosine at residue 309 in this motif is phosphorylated upon co-crosslinking with surface immunoglobulin; mutation of this residue aborts the inhibitory effect of FcγRIIB. This inhibition is directly coupled to signalling mediated through Ig-α and Ig-β as evidenced by chimaeric IgM/α and IgM/β molecules. The 13-residue motif in FcyRIIB controls lymphocyte activation by inhibiting a Ca2+ sig-nalling pathway triggered through ARH-1 motifs as a result of recruitment of novel SH2-containing proteins that interact with this FcγRIIB cytoplasmic motif.

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Authors and Affiliations

  1. DeWitt Wallace Research Laboratory, Sloan–Kettering Institute, 1275 York Avenue, New York, New York, 10021, USA

    Tatsushi Muta & Jeffrey V. Ravetch

  2. The Rockefeller University, 1230 York Avenue, New York, New York, 10021, USA

    Ziva Misulovin, Mercedes Sanchez & Michel C. Nussenzweig

  3. Department of Cardiovascular Molecular Biology, Lederle Laboratories, 401 North Middletown Road, Pearl River, New York, 10965, USA

    Tomohiro Kurosaki

Authors
  1. Tatsushi Muta
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  2. Tomohiro Kurosaki
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  3. Ziva Misulovin
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  4. Mercedes Sanchez
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  5. Michel C. Nussenzweig
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  6. Jeffrey V. Ravetch
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Muta, T., Kurosaki, T., Misulovin, Z. et al. A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling. Nature 368, 70–73 (1994). https://doi.org/10.1038/368070a0

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