Regulation of B cell activation balances effective antimicrobial responses with protection from autoimmunity and lymphoma. CD40 and CD95 are tumor necrosis factor receptor (TNFR) superfamily molecules signaling activation and apoptosis, respectively, in B cells. Activation of B cells through CD40 signaling increases surface expression of CD95, sensitizing cells to apoptosis, yet sustained CD40 signaling rescues B cells from CD95 killing. We found that CD40 signaling blocked caspase activation, thus rescuing B cells from apoptosis. CD40 rescue from CD95-induced apoptosis was dependent on the adaptor protein TRAF6 and the PI3 kinase-Akt pathway, but was independent of new protein synthesis or NF-kappaB activation.

Benson RJ, Hostager BS, Bishop GA. Rapid CD40-mediated rescue from CD95-induced apoptosis requires TNFR-associated factor-6 and PI3K. Eur J Immunol. 2006 Sep;36(9):2535-43. PubMed PMID: 16897814.