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J. Biol. Chem., Vol. 279, Issue 51, 53222-53231, December 17, 2004

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Role of Tumor Necrosis Factor (TNF) Receptor-associated Factor 2 (TRAF2) in Distinct and Overlapping CD40 and TNF Receptor 2/CD120b-mediated B Lymphocyte Activation^*

Melissa E. Munroe and Gail A. Bishop¶||

From the Departments of Microbiology and Internal Medicine, The University of Iowa and ^¶Veterans Affairs Medical Center, Iowa City, Iowa 52242

Members of the tumor necrosis factor receptor (TNFR) family play a variety of roles in the regulation of lymphocyte activation. An important TNFR family member for B cell activation is CD40. CD40 signals stimulate B cell TNF- secretion, which subsequently signals via TNFR2 (CD120b) to enhance B cell activation. Although the function of the pro-apoptotic and pro-inflammatory receptor TNFR1 (CD120a) has been the subject of much research, less is understood about the distinct contributions of CD120b to cell activation and how it stimulates downstream events. Members of the tumor necrosis factor receptor family bind various members of the cytoplasmic adapter protein family, the tumor necrosis factor receptor-associated factors (TRAFs), during signaling. Both CD40 and CD120b bind TNF receptor-associated factor 2 (TRAF2) upon ligand stimulation. Wild type and TRAF2-deficient B cells expressing CD40 or the hybrid molecule (human) CD40 (mouse)-CD120b were examined. CD40- and CD120b-mediated IgM secretion were partly TRAF2-dependent, but only CD40 required TRAF2 for c-Jun N-terminal kinase activation. CD40 and CD120b used primarily divergent mechanisms to activate NF-B, exemplifying how TNFR family members can use diverse mechanisms to mediate similar downstream events.

Received for publication, September 13, 2004

^* This work was supported by NIH Grants AI28847, AI49993, and CA099997 and a VA Career Award (to G. A. B.) and by NIH Training Grants AI07343 and AI07260 (to M. E. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: 2193B MERF, Dept. of Microbiology, University of Iowa, Iowa City, IA 52242. Tel.: 319-335-7945; Fax: 319-335-9006; E-mail: gail-bishop{at}uiowa.edu.

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