Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
Immunity. 2021 Oct 12;54(10):2245-2255.e4. doi: 10.1016/j.immuni.2021.08.003. Epub 2021 Aug 30.
BCL6 is required for development of follicular T helper (Tfh) cells to support germinal center (GC) formation. However, it is not clear what unique functions programmed by BCL6 can explain its absolute essentiality in T cells for GC formation. We found that ablation of one Bcl6 allele did not appreciably alter early T cell activation and follicular localization but inhibited GC formation and Tfh cell maintenance. BCL6 impinged on Tfh calcium signaling and also controlled Tfh entanglement with and CD40L delivery to B cells. Amounts of BCL6 protein and nominal frequencies of Tfh cells markedly changed within hours after strengths of T-B cell interactions were altered in vivo, while CD40L overexpression rectified both defective GC formation and Tfh cell maintenance because of the BCL6 haploinsufficiency. Our results reveal BCL6 functions in Tfh cells that are essential for GC formation and suggest that BCL6 helps maintain Tfh cell phenotypes in a T cell non-autonomous manner.
BCL6 对于滤泡辅助性 T 细胞（Tfh）的发育以支持生发中心（GC）的形成是必需的。然而，BCL6 所编程的独特功能尚不清楚，这些功能可以解释其在 T 细胞中对于 GC 形成的绝对必要性。我们发现，敲除一个 Bcl6 等位基因不会显著改变 T 细胞的早期激活和滤泡定位，但会抑制 GC 的形成和 Tfh 细胞的维持。BCL6 影响 Tfh 钙信号转导，并控制 Tfh 与 B 细胞的纠缠和 CD40L 的传递。在体内改变 T-B 细胞相互作用的强度后，BCL6 蛋白的数量和 Tfh 细胞的名义频率在数小时内发生显著变化，而 CD40L 的过表达纠正了 GC 形成和 Tfh 细胞维持的缺陷，因为 BCL6 杂合不足。我们的研究结果揭示了 BCL6 在 Tfh 细胞中的功能，这些功能对于 GC 的形成是必需的，并表明 BCL6 以非自主的方式帮助维持 Tfh 细胞表型。
