AUTHOR=Yang Lingtao , Chen Wei , Li Li , Xiao Yueyue , Fan Shilin , Zhang Quan , Xia Tian , Li Mengjie , Hong Yazhen , Zhao Tongjin , Li Qiyuan , Liu Wen-Hsien , Xiao Nengming 

TITLE=Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell Death

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.722273

DOI=10.3389/fimmu.2021.722273

ISSN=1664-3224

ABSTRACT=<p>Follicular helper T (T<sub>FH</sub>) cells are specialized CD4<sup>+</sup> helper T cells that provide help to B cells in humoral immunity. However, the molecular mechanism underlying generation of T<sub>FH</sub> cells is incompletely understood. Here, we reported that Damage-specific DNA binding protein 1 (Ddb1) was required for expansion of CD4<sup>+</sup> helper T cells including T<sub>FH</sub> and Th1 cells, germinal center response, and antibody response to acute viral infection. <italic>Ddb1</italic> deficiency in activated CD4<sup>+</sup> T cells resulted in cell cycle arrest at G2-M phase and increased cell death, due to accumulation of DNA damage and hyperactivation of ATM/ATR-Chk1 signaling. Moreover, mice with deletion of both <italic>Cul4a</italic> and <italic>Cul4b</italic> in activated CD4<sup>+</sup> T cells phenocopied <italic>Ddb1</italic>-deficient mice, suggesting that E3 ligase-dependent function of Ddb1 was crucial for genome maintenance and helper T-cell generation. Therefore, our results indicate that Ddb1 is an essential positive regulator in the expansion of CD4<sup>+</sup> helper T cells.</p>