TRAF2 IS ESSENTIAL FOR JNK BUT NOT NF-KAPPA-B ACTIVATION AND REGULATES LYMPHOCYTE-PROLIFERATION AND SURVIVAL

TRAF2 is believed to mediate the activation of NF-kappa B and JNK indu ced by the tumor necrosis factor receptor (TNFR) superfamily, which el icits pleiotropic responses in lymphocytes. We have investigated the p hysiological roles of TRAF2 in these processes by expressing a lymphoc yte-specific dominant negative form of TRAF2, thereby blocking this pr otein's effector function. We find that the TNFR superfamily signals r equire TRAF2 for activation of JNK but not NF-kappa B. In addition, we show that TRAF2 induces NF-kappa B-independent anti-apoptotic pathway s during TNF-induced apoptosis. Inhibition of TRAF2 leads to splenomeg aly, lymphadenopathy, and an increased number of B cells. These findin gs indicate that TRAF2 is involved in the regulation of lymphocyte fun ction and growth in vivo.