PMID- 10352240 OWN - NLM STAT- MEDLINE DCOM- 19990616 LR - 20181201 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 162 IP - 11 DP - 1999 Jun 1 TI - Cutting edge: contrasting roles of TNF receptor-associated factor 2 (TRAF2) and TRAF3 in CD40-activated B lymphocyte differentiation. PG - 6307-11 AB - 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. FAU - Hostager, B S AU - Hostager BS AD - Department of Microbiology, University of Iowa, VA Medical Center, Iowa City 52242, USA. FAU - Bishop, G A AU - Bishop GA LA - eng GR - AI28847/AI/NIAID NIH HHS/United States GR - CA66570/CA/NCI NIH HHS/United States GR - DK25295/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (CD40 Antigens) RN - 0 (Proteins) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (TNF Receptor-Associated Factor 2) RN - 0 (TNF Receptor-Associated Factor 3) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antibody Formation/genetics/immunology MH - B-Lymphocytes/*cytology/*immunology/metabolism MH - CD40 Antigens/genetics/metabolism/*physiology MH - Cell Differentiation/genetics/immunology MH - Cell Line MH - Humans MH - Lymphocyte Activation MH - Mice MH - Molecular Sequence Data MH - Protein Binding/immunology MH - Protein Biosynthesis MH - Proteins/genetics/metabolism/*physiology MH - Receptors, Tumor Necrosis Factor/*physiology MH - TNF Receptor-Associated Factor 2 MH - TNF Receptor-Associated Factor 3 MH - Transfection/immunology MH - Tumor Cells, Cultured EDAT- 1999/06/03 00:00 MHDA- 1999/06/03 00:01 CRDT- 1999/06/03 00:00 PHST- 1999/06/03 00:00 [pubmed] PHST- 1999/06/03 00:01 [medline] PHST- 1999/06/03 00:00 [entrez] PST - ppublish SO - J Immunol. 1999 Jun 1;162(11):6307-11.