B Cell Receptor and BAFF Receptor Signaling Regulation of B Cell Homeostasis

Abstract

B lymphocyte homeostasis depends on tonic and induced BCR signaling and receptors sensitive to trophic factors, such as B cell-activating factor receptor (BAFF-R or BR3) during development and maintenance. This review will discuss growing evidence suggesting that the signaling mechanisms that maintain B cell survival and metabolic fitness during selection at transitional stages and survival after maturation rely on cross-talk between BCR and BR3 signaling. Recent findings have also begun to unravel the molecular mechanisms underlying this crosstalk. In this review I also propose a model for regulating the amplitude of BCR signaling by a signal amplification loop downstream of the BCR involving Btk and NF-κB that may facilitate BCR-dependent B cell survival as well as its functional coupling to BR3 for the growth and survival of B lymphocytes.