Submitted August 27, 2008
Accepted February 2, 2009
A critical role of TAK1 in B cell receptor-mediated NF-
B activation
James Schuman, Yuhong Chen, Andrew Podd, Mei Yu, Hong-Hsing Liu, Renren Wen, Zhijian J. Chen, and Demin Wang*
Blood Research Institute, the BloodCenter of Wisconsin, Milwaukee, WI, United States
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, United States
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, United States
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, United States
* Corresponding author; email: demin.wang{at}bcw.edu.
The kinase TAK1 is essential for T cell receptor (TCR)-mediated NF-
B activation and T cell development. However, the role of TAK1 in B cell receptor (BCR)-mediated NF-B activation and B cell development is not clear. Here we show that B cell-specific deletion of TAK1 impaired the transition from transitional type 2 to mature follicular (FO) B cells and caused a marked decrease of marginal zone (MZ) B cells. TAK1-deficient B cells exhibited an increase of BCR-induced apoptosis and impaired proliferation in response to BCR ligation. Importantly, TAK1-deficient B cells failed to activate NF-B following BCR stimulation. Thus, TAK1 is critical for B cell maturation and BCR-induced NF-B activation.
