FcγRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation

These studies investigate how interactions between the BCR and Fc gamma RIIB affect B lymphocyte stimulator ( BLyS) receptor 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 Fc gamma RIIB coaggregation dampens BCR-induced BLyS receptor up-regulation. This cross-regulation requires BCR and Fc gamma RIIB coligation, and optimal action relies on the Src-homology-2 (SH2) containing inositol 5 phosphase-1 (SHIP1). Subsequent to Fc gamma RIIB/BCR coaggregation, the survival promoting actions of BLyS are attenuated, reflecting reduced BLyS receptor signaling capacity in terms of Pim 2 maintenance, noncanonical NF-kappa B activation, and Bcl-xL levels. These findings link the negative regulatory functions of Fc gamma RIIB with BLyS-mediated B-cell survival. ( Blood. 2009; 113: 1464-1473)