Early Growth Response Genes 2 and 3 Regulate the Expression of Bcl6 and Differentiation of T Follicular Helper Cells.
Early Growth Response Genes 2 and 3 Regulate the Expression of Bcl6 and Differentiation of T Follicular Helper Cells.
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DOI：
10.1074/jbc.m114.634816
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发表时间：
2015-08-14
期刊：
影响因子：
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通讯作者：
Wang P
中科院分区：
文献类型：
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作者：
Ogbe A;Miao T;Symonds AL;Omodho B;Singh R;Bhullar P;Li S;Wang P
背景：T滤泡辅助细胞（Tfh）是B细胞抗病毒反应的必需细胞，需要B细胞淋巴瘤6（BCL 6）。结果：早期生长反应基因2（EGR 2）和EGR 3对Bcl 6和Tfh细胞具有内在调节作用。结论：EGR 2和EGR 3是BCL 6介导的Tfh发育的新调控因子。意义：除了控制炎症外，EGR 2和EGR 3还在抗病毒免疫应答期间调节Tfh功能。T滤泡辅助（Tfh）细胞支持B细胞分化为浆细胞和在生殖中心（GC）中产生高亲和力抗体，并且Tfh分化需要B细胞淋巴瘤6（BCL 6）的功能。我们现在已经发现，早期生长反应基因2（EGR 2）和EGR 3直接调节Bcl 6在Tfh细胞中的表达，这是它们在调节GC形成中的功能所必需的。在缺乏EGR 2和EGR 3的情况下，Tfh细胞中BCL 6的表达是缺陷的，导致Tfh细胞的分化受损，导致病毒感染后不能形成GC和抗病毒抗体产生缺陷。在EGFR 2/3缺陷型CD 4 T细胞中，BCL 6的增强表达部分恢复了Tfh分化和GC形成，以响应病毒感染。我们的研究结果证明了EGFR 2/3的一种新功能，它对Tfh细胞发育和Tfh细胞介导的B细胞免疫应答非常重要。
Background: T follicular helper (Tfh) cells are essential for B cell responses against viruses and require B cell lymphoma 6 (BCL6). Results: Early growth response gene 2 (EGR2) and EGR3 intrinsically regulate Bcl6 and Tfh cells. Conclusion: EGR2 and -3 are novel regulators of BCL6-mediated Tfh development. Significance: In addition to controlling inflammation, EGR2 and -3 regulate Tfh function during antiviral immunoresponses. T follicular helper (Tfh) cells support differentiation of B cells to plasma cells and high affinity antibody production in germinal centers (GCs), and Tfh differentiation requires the function of B cell lymphoma 6 (BCL6). We have now discovered that early growth response gene 2 (EGR2) and EGR3 directly regulate the expression of Bcl6 in Tfh cells, which is required for their function in regulation of GC formation. In the absence of EGR2 and -3, the expression of BCL6 in Tfh cells is defective, leading to impaired differentiation of Tfh cells, resulting in a failure to form GCs following virus infection and defects in production of antiviral antibodies. Enforced expression of BCL6 in EGR2/3-deficient CD4 T cells partially restored Tfh differentiation and GC formation in response to virus infection. Our findings demonstrate a novel function of EGR2/3 that is important for Tfh cell development and Tfh cell-mediated B cell immune responses.