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 proteins appear to be important components of the CD40 signal transduction complex, 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 cells transfected with inducible TRAF and dominant-negative TRAF cDNAs. We find that binding of TRAF2 and TRAF3 to CD40 is not required for the induction 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 positive role in B cell differentiation, and this activity is apparent even when its binding site on CD40 is disrupted.
Hostager
B S
BS
Department of Microbiology, University of Iowa, VA Medical Center, Iowa City 52242, USA.
Bishop
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3