Rad9 Is Required for B Cell Proliferation and Immunoglobulin Class Switch Recombination |
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| Authors: | Lili An Yulan Wang Yuheng Liu Xiao Yang Chunchun Liu Zhishang Hu Wei He Wenxia Song Haiying Hang |
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| Institution: | From the ‡National Laboratory of Biomacromolecules, and ;the §Center for Computational and Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China and ;the ¶Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742 |
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| Abstract: | B cell maturation and B cell-mediated antibody response require programmed DNA modifications such as the V(D)J recombination, the immunoglobulin (Ig) class switch recombination, and the somatic hypermutation to generate functional Igs. Many protein factors involved in DNA damage repair have been shown to be critical for the maturation and activation of B cells. Rad9 plays an important role in both DNA repair and cell cycle checkpoint control. However, its role in Ig generation has not been reported. In this study, we generated a conditional knock-out mouse line in which Rad9 is deleted specifically in B cells and investigated the function of Rad9 in B cells. The Rad9−/− B cells isolated from the conditional knock-out mice displayed impaired growth response and enhanced DNA lesions. Impaired Ig production in response to immunization in Rad9−/− mice was also detected. In addition, the Ig class switch recombination is deficient in Rad9−/− B cells. Taken together, Rad9 plays dual roles in generating functional antibodies and in maintaining the integrity of the whole genome in B cells. |
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| Keywords: | Antibodies Apoptosis Cell Cycle Cell Division DNA Repair B Cells Rad9 Class Switch Recombination Genome Integrity Proliferation |
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