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

Research output: Contribution to journalArticlepeer-review

432 Citations (Scopus)


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
Issue number6466
Publication statusPublished - 1994 Jan 1

ASJC Scopus subject areas

  • General


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