Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses
Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses
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铁依赖性组蛋白 3 赖氨酸 9 去甲基化控制 B 细胞增殖和体液免疫反应
DOI：
10.1038/s41467-019-11002-5
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发表时间：
2019-07-03
影响因子：
16.6
通讯作者：
Zhang, Xiaoren
中科院分区：
文献类型：
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作者：
Jiang, Yuhang;Li, Cuifeng;Zhang, Xiaoren
微量元素在人体健康中发挥着重要作用，但对其在体液免疫中的作用却知之甚少。在这里，我们展示了铁在诱导细胞周期蛋白E和B细胞增殖中的重要作用。我们发现，与铁正常的对照组相比，铁缺乏的人对麻疹疫苗的抗体反应显著降低。铁缺乏的小鼠也表现出T依赖或T非依赖的抗原特异性抗体反应减弱。我们发现铁是B细胞增殖所必需的，缺铁和α-酮戊二酸抑制都能抑制B细胞活化时细胞周期蛋白E_1的诱导和S时相的进入。最后，我们证明了三种去甲基酶Kdm2b、KDM3B和KDM4C负责组蛋白3赖氨酸9(H3K9)在细胞周期蛋白E1启动子上的去甲基化、细胞周期蛋白E1诱导和B细胞增殖。因此，我们的数据揭示了H3K9去甲基化在B细胞增殖中的关键作用，以及铁在体液免疫中的重要性。
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.