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

Tatsushi Muta, Tomohiro Kurosaki, Ziva Misulovin, Mercedes Sanchez, Michel C. Nussenzweig, Jeffrey V. Ravetch

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Abstract

THE Fc receptor on B lymphocytes, FcγRIIB (β1 isoform), helps to modulate B-cell activation triggered by the surface immunoglobulin complex 1,2. 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.

Original languageEnglish
Pages (from-to)70-73
Number of pages4
JournalNature
Volume368
Issue number6466
DOIs
Publication statusPublished - 1994 Jan 1

ASJC Scopus subject areas

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    Muta, T., Kurosaki, T., Misulovin, Z., Sanchez, M., Nussenzweig, M. C., & Ravetch, J. V. (1994). A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling. Nature, 368(6466), 70-73. https://doi.org/10.1038/368070a0