Targeted disruption ofTraf5gene causes defects in CD40- and CD27-mediated lymphocyte activation

• DOI: 10.1073/pnas.96.17.9803
• Publication Date: 2002-07-26T14:41:48Z
• Authors: Hiroyasu Nakano; Sachiko Sakon; Haruhiko Koseki; Toshitada Takemori; Kurisu Tada; Mitsuru Matsumoto; Eiko Munechika; Tsuyoshi Sakai; Takuji Shirasawa; Hisaya Akiba; Tetsuji Kobata; Sybil M. Santee; Carl F. Ware; Paul D. Rennert; Masaru Taniguchi; Hideo Yagita; Ko Okumura
• Keywords: Mice, Knockout; TNF Receptor-Associated Factor 5; Membrane Glycoproteins; CD40 Ligand; JNK Mitogen-Activated Protein Kinases; NF-kappa B; Proteins; Lymphocyte Activation; Tumor Necrosis Factor Receptor Superfamily, Member 7; Enzyme Activation; Mice; 03 medical and health sciences; 0302 clinical medicine; Calcium-Calmodulin-Dependent Protein Kinases; Animals; CD40 Antigens; Mitogen-Activated Protein Kinases

TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-κB and c-Jun NH2-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 TRAF5in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-κB or c-Jun NH2-terminal kinase/stress-activated protein kinase by tumor necrosis factor, CD27, and CD40 was not abrogated intraf5−/−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 vitroIg production oftraf5−/−B cells stimulated with anti-CD40 plus IL-4 was reduced substantially. CD27-mediated costimulatory signal also was impaired intraf5−/−T cells. Collectively, these results demonstrate that TRAF5 is involved in CD40- and CD27-mediated signaling.