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

doi:10.1016/S1074-7613(00)80509-9

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

Pediatric Blood & Marrow Transplant & Cellular Therapy

Research output: Contribution to journal › Article › peer-review

112 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 language	English (US)
Pages (from-to)	49-58
Number of pages	10
Journal	Immunity
Volume	7
Issue number	1
DOIs	https://doi.org/10.1016/S1074-7613(00)80509-9
State	Published - 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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SDG 3 Good Health and Well-being

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10.1016/S1074-7613(00)80509-9

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@article{a94a192b42db4c5b8e2e0262188cc046,

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

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.",

author = "Hippen, \{Keli L.\} and Buhl, \{Anne Mette\} and Daniele D'Ambrosio and Kazuhiro Nakamura and Christoph Persin and Cambier, \{John C.\}",

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.",

year = "1997",

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doi = "10.1016/S1074-7613(00)80509-9",

language = "English (US)",

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T1 - FcγRIIB1 inhibition of BCR-mediated phosphoinositide hydrolysis and Ca2+ mobilization is integrated by CD19 dephosphorylation

AU - Hippen, Keli L.

AU - Buhl, Anne Mette

AU - D'Ambrosio, Daniele

AU - Nakamura, Kazuhiro

AU - Persin, Christoph

AU - Cambier, John C.

N1 - 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.

PY - 1997/7

Y1 - 1997/7

N2 - 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.

AB - 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.

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