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FcgammaRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation.

ABSTRACT: These studies investigate how interactions between the BCR and FcgammaRIIB affect B lymphocyte stimulator (BLyS) recep-tor expression and signaling. Previous studies showed that BCR ligation up-regulates BLyS binding capacity in mature B cells, reflecting increased BLyS receptor levels. Here we show that FcgammaRIIB coaggregation dampens BCR-induced BLyS receptor up-regulation. This cross-regulation requires BCR and FcgammaRIIB coligation, and optimal action relies on the Src-homology-2 (SH2)-containing inositol 5 phosphase-1 (SHIP1). Subsequent to FcgammaRIIB/BCR coaggregation, the survival promoting actions of BLyS are attenuated, reflecting reduced BLyS receptor signaling capacity in terms of Pim 2 maintenance, noncanonical NF-kappaB activation, and Bcl-xL levels. These findings link the negative regulatory functions of FcgammaRIIB with BLyS-mediated B-cell survival.

SUBMITTER: Crowley JE

PROVIDER: S-EPMC2644074 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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FcgammaRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation.

Crowley Jenni E JE Stadanlick Jason E JE Cambier John C JC Cancro Michael P MP

Blood 20080912 7

These studies investigate how interactions between the BCR and FcgammaRIIB affect B lymphocyte stimulator (BLyS) recep-tor expression and signaling. Previous studies showed that BCR ligation up-regulates BLyS binding capacity in mature B cells, reflecting increased BLyS receptor levels. Here we show that FcgammaRIIB coaggregation dampens BCR-induced BLyS receptor up-regulation. This cross-regulation requires BCR and FcgammaRIIB coligation, and optimal action relies on the Src-homology-2 (SH2)-co ...[more]

PMID: 18791164

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