A critical role of TAK1 in B-cell receptor–mediated nuclear factor κB activation

Author:

Schuman James12,Chen Yuhong1,Podd Andrew12,Yu Mei13,Liu Hong-Hsing4,Wen Renren1,Chen Zhijian J.45,Wang Demin12

Affiliation:

1. Blood Research Institute, BloodCenter of Wisconsin, Milwaukee;

2. Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee;

3. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China; and

4. Department of Molecular Biology and

5. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas

Abstract

AbstractThe kinase TAK1 is essential for T-cell receptor (TCR)–mediated nuclear factor κB (NF-κB) activation and T-cell development. However, the role of TAK1 in B-cell receptor (BCR)–mediated NF-κB 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-κB after BCR stimulation. Thus, TAK1 is critical for B-cell maturation and BCR-induced NF-κB activation.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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