Ogbe Ane, Miao Tizong, Symonds Alistair L J, Omodho Becky, Singh Randeep, Bhullar Punamdip, Li Suling, Wang Ping
From the Division of Biosciences, Department of Life Sciences, Brunel University, Kingston Lane, UB8 3PH, United Kingdom and the Blizard Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AD, United Kingdom.
the Blizard Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AD, United Kingdom.
J Biol Chem. 2015 Aug 14;290(33):20455-65. doi: 10.1074/jbc.M114.634816. Epub 2015 May 15.
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.
滤泡辅助性T（Tfh）细胞支持B细胞分化为浆细胞，并在生发中心（GC）产生高亲和力抗体，而Tfh细胞分化需要B细胞淋巴瘤6（BCL6）发挥作用。我们现已发现，早期生长反应基因2（EGR2）和EGR3直接调节Tfh细胞中Bcl6的表达，这是它们调节GC形成功能所必需的。在缺乏EGR2和EGR3的情况下，Tfh细胞中BCL6的表达存在缺陷，导致Tfh细胞分化受损，进而在病毒感染后无法形成GC，且抗病毒抗体产生存在缺陷。在EGR2/3缺陷的CD4 T细胞中强制表达BCL6可部分恢复Tfh细胞分化和对病毒感染的GC形成。我们的研究结果证明了EGR2/3的一种新功能，该功能对Tfh细胞发育和Tfh细胞介导的B细胞免疫反应很重要。
