Ascorbic acid promotes plasma cell differentiation through enhancing TET2/3-mediated DNA demethylation

Plasma cells are critical sources of 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 un-explored. In this study, we show that ascorbic acid (Vitamin C), an essential nutrient, was able to promote plasma cell differentiation and humoral immune response via enhancing Tet 2/3-mediated DNA demethylation. A short-term ascorbic acid treatment during B cell activation, had persistent effects on later plasma cell differentiation. Conversely, ascorbic acid deficiency in vivo blocked plasma cell differentiation and attenuated humoral immune response following antigen immunization. We further demonstrated that such effects of ascorbic acid on B cells redundantly required DNA methylcytosine oxidases Tet2 and Tet3. Our study thus for the first time revealed a previously uncharacterized link between nutrients and epigenetic regulation of plasma cell differentiation and humoral immune response.