Signalling crosstalk in B cells: managing worth and need

The B cell receptor (BCR) and the receptor for B cell-activating factor (BAFFR) have complementary roles in B cells: BCR signals provide a cell-intrinsic measure of suitability for negative or positive selection, whereas BAFFR responds to homeostatic demands based on a cell-extrinsic measure of the size of the mature B cell pool. Because continuous signals from both receptors are required for B cell survival, it is probable that there are mechanisms to integrate the selective and homeostatic signals from these receptors. In this Opinion article, I describe recent evidence to indicate that crosstalk between the downstream biochemical pathways of these receptors mediates this interdependence, such that BCR signals generate a limiting substrate for BAFFR signal propagation.