Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses

Yuhang Jiang, Cuifeng Li, Qian Wu, Peng An, Laiquan Huang, Jia Wang, Chen Chen, Xi Chen, Fan Zhang, Li Ma, Sanhong Liu, Hanqing He, Shuyun Xie, Yangbai Sun, Hanshao Liu, Yu Zhan, Yu Tao, Zhi Liu, Xiaohua Sun, Yiming Hu, Qi Wang, Deji Ye, Jie Zhang, Shanhua Zou, Ying Wang, Gang Wei, Yongzhong Liu, Yufang Shi, Y. Eugene Chin, Yongqiang Hao, Fudi Wang () and Xiaoren Zhang ()
Additional contact information
Yuhang Jiang: Guangzhou Medical University
Cuifeng Li: Guangzhou Medical University
Qian Wu: Zhejiang University School of Medicine
Peng An: Zhejiang University School of Medicine
Laiquan Huang: The First Affiliated Hospital of Wannan Medical College
Jia Wang: Zhejiang University School of Medicine
Chen Chen: Zhongshan Hospital Fudan University
Xi Chen: Guangzhou Medical University
Fan Zhang: Zhejiang University School of Medicine
Li Ma: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Sanhong Liu: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Hanqing He: Zhejiang Provincial Center for Disease Control and Prevention
Shuyun Xie: Zhejiang Provincial Center for Disease Control and Prevention
Yangbai Sun: Zhejiang Provincial Center for Disease Control and Prevention
Hanshao Liu: Guangzhou Medical University
Yu Zhan: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Yu Tao: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Zhi Liu: Guangzhou Medical University
Xiaohua Sun: Guangzhou Medical University
Yiming Hu: Guangzhou Medical University
Qi Wang: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Deji Ye: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Jie Zhang: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Shanhua Zou: Zhongshan Hospital Fudan University
Ying Wang: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Gang Wei: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Yongzhong Liu: Shanghai Jiao-Tong University School of Medicine
Yufang Shi: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Y. Eugene Chin: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Yongqiang Hao: Shanghai JiaoTong University School of Medicine
Fudi Wang: Zhejiang University School of Medicine
Xiaoren Zhang: Guangzhou Medical University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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 α-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.

Date: 2019
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DOI: 10.1038/s41467-019-11002-5

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