FcgammaRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation.
نویسندگان
چکیده
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.
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عنوان ژورنال:
- Blood
دوره 113 7 شماره
صفحات -
تاریخ انتشار 2009