Cutting edge: Contrasting roles of TNF receptor-associated factor 2 (TRAF2) and TRAF3 in CD40-activated B lymphocyte differentiation

In B lymphocytes, CD40 signals contribute to the activation of Ab secretion , isotype switching, T cell costimulation, and immunological memory. TRAF p roteins appear to be important components of the CD40 signal transduction c omplex, but their roles in the activation of B cell effector functions are poorly understood. We examined the contributions of TNF receptor-associated factor 2 (TRAF2) and TRAF3 to CD40-activated differentiation in mouse B ce lls transfected with inducible TRAF and dominant-negative TRAF cDNAs. We fi nd that binding of TRAF2 and TRAF3 to CD40 is not required for the inductio n of Ab secretion, but that both TRAF molecules can regulate the activation process. We demonstrate a negative regulatory role for TRAF3 and that this activity is dependent on the availability of an intact TRAF3-binding site in the cytoplasmic,domain of CD40, In contrast, TRAF2 appears to play a pos itive role in B cell differentiation, and this activity is apparent even wh en its binding site on CD40 is disrupted.