Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 17; pp. 9803 - 9808
• Main Authors: Nakano, H, Sakon, S, Koseki, H, Takemori, T, Tada, K, Matsumoto, M, Munechika, E, Sakai, T, Shirasawa, T, Akiba, H, Kobata, T, Santee, S M, Ware, C F, Rennert, P D, Taniguchi, M, Yagita, H, Okumura, K
• Format: Journal Article
• Language: English
• Published: United States National Acad Sciences 17-08-1999; National Academy of Sciences; The National Academy of Sciences
• Subjects: Animals; Biological Sciences; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; CD40 Antigens - immunology; CD40 Ligand; Enzyme Activation; Genes; Immunology; JNK Mitogen-Activated Protein Kinases; Leukocytes; Lymphocyte Activation; Membrane Glycoproteins - immunology; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases; NF-kappa B - metabolism; Proteins; Proteins - genetics; TNF Receptor-Associated Factor 5; Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.17.9803

TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-κB and c-Jun NH 2 -terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-β receptor. To investigate the functional role of TRAF5 in vivo , we generated TRAF5-deficient mice by gene targeting. Activation of either NF-κB or c-Jun NH 2 -terminal kinase/stress-activated protein kinase by tumor necrosis factor, CD27, and CD40 was not abrogated in traf5 −/− mice. However, traf5 −/− B cells showed defects in proliferation and up-regulation of various surface molecules, including CD23, CD54, CD80, CD86, and Fas in response to CD40 stimulation. Moreover, in vitro Ig production of traf5 −/− B cells stimulated with anti-CD40 plus IL-4 was reduced substantially. CD27-mediated costimulatory signal also was impaired in traf5 −/− T cells. Collectively, these results demonstrate that TRAF5 is involved in CD40- and CD27-mediated signaling.