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.

Details

Title
Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses
Author
Jiang, Yuhang 1   VIAFID ORCID Logo  ; Li, Cuifeng 1 ; Wu, Qian 2   VIAFID ORCID Logo  ; Peng, An 2 ; Huang, Laiquan 3   VIAFID ORCID Logo  ; Wang, Jia 2 ; Chen, Chen 4 ; Chen, Xi 1 ; Zhang, Fan 2 ; Li, Ma 5 ; Liu, Sanhong 6 ; He, Hanqing 7 ; Xie, Shuyun 7 ; Sun, Yangbai 7 ; Liu, Hanshao 1 ; Yu, Zhan 6 ; Yu, Tao 6 ; Liu, Zhi 1 ; Sun, Xiaohua 1 ; Hu, Yiming 1 ; Wang, Qi 6 ; Ye, Deji 6 ; Zhang, Jie 6 ; Zou, Shanhua 4 ; Wang, Ying 6 ; Wei, Gang 5 ; Liu, Yongzhong 8   VIAFID ORCID Logo  ; Shi, Yufang 6   VIAFID ORCID Logo  ; Chin, Y Eugene 6 ; Hao, Yongqiang 9 ; Wang, Fudi 2   VIAFID ORCID Logo  ; Zhang, Xiaoren 1 

1  Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China 
2  The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China; Department of Nutrition, Precision Nutrition Innovation Center, School of Public Health, Zhengzhou University, Zhengzhou, China 
3  Department of Hematology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China 
4  Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, China 
5  Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China 
6  CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China 
7  Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China 
8  Shanghai Cancer Institute, Shanghai Jiao-Tong University School of Medicine, Shanghai, China 
9  Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China 
Pages
1-15
Publication year
2019
Publication date
Jul 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11002-5
ProQuest document ID
2251709009
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.