Tonic B cell antigen receptor signals supply an NF-kappa substrate, p100, for prosurvival BLyS signaling

Survival of transitional and mature B cells requires both the B cell antigen receptor (BCR) and BLyS receptor 3 (BR3), suggesting that these receptors send signals that are non-redundant or that they exhibit a downstream connection. Here we show that BCR signaling induces production of the non-classical NF-kappaB pathway substrate p100, which is required for transmission of BR3 signals and thus B cell survival. The capacity for sustained p100 production emerges during transitional B cell differentiation, the point where BCR signals mediate survival, rather than negative selection. These findings reveal a molecular mechanism for the reliance of primary B cells on continuous BR3 and BCR signaling, as well as for the gradual resistance to negative selection acquired during B cell maturation.