Survival signaling in resting B cells

The survival of mature resting B cells in the periphery depends on signaling from the B-cell receptor (BCR) and the B-cell activating factor of the TNF family receptor (BAFF-R). Engagement of both receptors promotes NF-κB activity, which contributes to B-cell survival through different pathways. BCR signaling leads to activation of the inhibitor of NF-κB kinase (IKK) complex via Carma1, Bcl10 and MALT1, whereas BAFF-R engagement promotes processing of NF-κB2 protein p100, which is dependent on NF-κB-inducing kinase (NIK) and IKKα. Proximal signaling intermediates are potentially common to both pathways. We suggest that BCR and BAFF-R survival signaling are mutually dependent. In addition, we propose that BAFF-R signaling enhances the expression of survival genes through direct chromatin modifications in NF-κB target gene promoters.