Submitted February 21, 2008
Accepted August 11, 2008
Fc
RIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor upregulation
Jenni E. Crowley, Jason E. Stadanlick, John C. Cambier, and Michael P. Cancro*
Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, CO, United States
* Corresponding author; email: cancro{at}mail.med.upenn.edu.
These studies investigate how interactions between the BCR and Fc
RIIB affect B lymphocyte stimulator (BLyS) receptor expression and signaling. Previous studies showed that BCR ligation upregulates BLyS binding capacity in mature B cells, reflecting increased BLyS receptor levels. Here we show that FcRIIB co-aggregation dampens BCR-induced BLyS receptor upregulation. This cross-regulation requires BCR and FcRIIB co-ligation, and optimal action relies on the SH2-containing inositol 5 phosphase-1 (SHIP1). Subsequent to FcRIIB/BCR co-aggregation, the survival promoting actions of BLyS are attenuated, reflecting reduced BLyS receptor signaling capacity in terms of Pim 2 maintenance, non-canonical NF-
B activation, and Bcl-xL levels. These findings link the negative regulatory functions of FcRIIB with BLyS-mediated B cell survival.
