Jiang, Y; Ma, Li; Liu, S; He, H; Xie, S; Sun, Y; Liu, H; Zhan, Yu; Tao, Yu; Liu, Zhi; Sun, X; Li, C; Hu, Y; Wang, Qi; Ye, D; Zhang, Jie; Zou, S; Wang, Y; Wei, G; Liu, Y; Shi, Y; Chin, YE; Wu, Q; Hao, Y; Wang, F; Zhang, X; An, P; Huang, L; Wang, Jia; Chen, C; Chen, Xi; Zhang, Fan; ,
Trace elements play important roles in human health, but little is known about their functions in humoral immunity. Here, we show an important role for iron in inducing cyclin E and B cell proliferation. We find that iron-deficient individuals exhibit a significantly reduced antibody response to the measles vaccine when compared to iron-normal controls. Mice with iron deficiency also exhibit attenuated T-dependent or T-independent antigen-specific antibody responses. We show that iron is essential for B cell proliferation; both iron deficiency and a-ketoglutarate inhibition could suppress cyclin E1 induction and S phase entry of B cells upon activation. Finally, we demonstrate that three demethylases, KDM2B, KDM3B and KDM4C, are responsible for histone 3 lysine 9 (H3K9) demethylation at the cyclin E1 promoter, cyclin E1 induction and B cell proliferation. Thus, our data reveal a crucial role of H3K9 demethylation in B cell proliferation, and the importance of iron in humoral immunity.
