Ascorbic Acid Promotes Plasma Cell Differentiation through Enhancing TET2/3-Mediated DNA Demethylation
Tuan Qi,
Mengmeng Sun,
Chao Zhang,
Pengda Chen,
Changchun Xiao,
Xing Chang
Affiliations
Tuan Qi
Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Joint Research Center of Hangzhou First Hospital Group and Westlake University, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
Mengmeng Sun
CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China
Chao Zhang
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Joint Research Center of Hangzhou First Hospital Group and Westlake University, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
Pengda Chen
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
Changchun Xiao
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
Xing Chang
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Joint Research Center of Hangzhou First Hospital Group and Westlake University, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Corresponding author
Summary: Plasma cells provide high-affinity antibodies against invading pathogens. Although transcriptional and epigenetic mechanisms have been extensively studied for plasma cell differentiation, how these mechanisms respond to environmental cues remains largely unexplored. In this study, we show that ascorbic acid (vitamin C), an essential nutrient, is able to promote plasma cell differentiation and humoral immune response by enhancing TET2/3-mediated DNA demethylation. Ascorbic acid treatment during B cell activation has persistent effects on later plasma cell differentiation by predisposing germinal center B cells toward the plasma cell lineage. Conversely, ascorbic acid deficiency in vivo blocks plasma cell differentiation and attenuates the humoral immune response following antigen immunization. We further demonstrate that such effects of ascorbic acid on plasma cell differentiation require DNA methylcytosine oxidases TET2 and TET3. Our study thus reveals a previously uncharacterized link between essential nutrients and epigenetic regulation of plasma cell differentiation and humoral immune response.
