Signaling by CD40 and its mimics in B cell activation

CD40 is a member of the growing tumor necrosis factor receptor (TNF-R) fami ly of molecules, and has been shown to play important roles in T cell-media ted 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 prese ntation, development of the germinal center, and the humoral memory respons e. Several distinct structural motifs in the CD40 cytoplasmic domain regula te 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 mi micked by several biological response modifiers, as well as by a viral onco protein encoded by the Epstein-Barr virus (EBV).