Signaling by CD40 and its mimics in B cell activation

CD40 is a member of the growing tumor necrosis factor receptor (TNF-R) family of molecules, and has been shown to play important roles in T cell-mediated B lymphocyte activation. Ligation of B cell CD40 by CD154 expressed on activated T cells stimulates B cell proliferation, differentiation, isotype switching, upregulation of surface molecules contributing to antigen presentation, development of the germinal center, and the humoral memory response. Several distinct structural motifs in the CD40 cytoplasmic domain regulate various CD40 signaling pathways, which involve both the TNF-R associated factors (TRAFs) and additional signaling proteins, and lead to activation of kinases and transcription factors. CD40-mediated B cell activation is mimicked by several biological response modifiers, as well as by a viral oncoprotein encoded by the Epstein-Barr virus (EBV).