FcγRIIB1 inhibition of BCR-mediated phosphoinositide hydrolysis and Ca2+ mobilization is integrated by CD19 dephosphorylation

Keli L. Hippen, Anne Mette Buhl, Daniele D'Ambrosio, Kazuhiro Nakamura, Christoph Persin, John C. Cambier

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

The B cell receptor for immunoglobulin G, FcγRIIB1, is a potent transducer of signals that block antigen-induced B cell activation. Coligation of FcγRIIB1 with B lymphocyte antigen receptors (BCR) causes premature termination of phosphoinositide hydrolysis and Ca2+ mobilization and inhibits proliferation. This inhibitory signal is mediated in part by phosphorylation of FcγRIIB1 and recruitment of phosphatases; however, the molecular target(s) of effectors is unknown. Here we report that FcγRIIB1 inhibition of BCR signaling is mediated in part by selective dephosphorylation of CD19, a BCR accessory molecule and coreceptor. CD19 dephosphorylation leads to failed CD19 association with phosphatidylinositol 3-kinase, and this in turn leads to termination of inositol-1,4,5- trisphosphate production, intracellular Ca2+ release, and Ca2+ influx. The results define a molecular circuit by which FcγRIIB signals block phosphoinositide hydrolysis.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalImmunity
Volume7
Issue number1
DOIs
StatePublished - Jul 1997

Bibliographical note

Funding Information:
Correspondence should be addressed to J. C. C. (e-mail: cambierj@ njc.org). This work was supported by grants from the United States Public Health Service. J. C. C. is an Ida and Cecil Green Professor of Cell Biology. A. M. B. is a fellow of the Leukemia Society of America. We thank W. Jensen and L. Pao for helpful advice and comments, and J. Franconi for secretarial assistance.

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