Bach2 regulates B cell survival to maintain germinal centers and promote B cell memory
Bach2 regulates B cell survival to maintain germinal centers and promote B cell memory
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Bach2 调节 B 细胞存活以维持生发中心并促进 B 细胞记忆
DOI：
10.1016/j.bbrc.2022.06.009
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发表时间：
2022-06-15
影响因子：
3.1
通讯作者：
Huang, Chuanxin
中科院分区：
文献类型：
--
作者：
Hu, Qianwen;Xu, Tingting;Huang, Chuanxin
转录因子Bach2是生发中心(GC)反应的重要调节因子，生发中心反应是产生高亲和力抗体和建立长期B细胞记忆所必需的。然而，Bach2控制GC程序的阶段以及这些过程背后的确切机制仍然知之甚少。在这项研究中，我们发现小鼠GC B细胞中Bach2基因的遗传消融损害了它们的存活和维持，以及记忆B细胞的形成。这些缺陷可以通过强制表达抗凋亡基因Bcl2来挽救。正如预期的那样，Bach2缺陷的GC B细胞在抗体亲和力成熟方面存在缺陷，但具有正常的体细胞超突变和免疫球蛋白基因的类开关重组。在机制上，Bach2通过直接抑制促凋亡基因Bim和一系列参与细胞应激反应和代谢过程的基因来控制GC程序。因此，我们的工作揭示了Bach2在GC生物学中的确切作用，并证明Bach2作为GC B细胞的关键生存调节因子，提供了GC B维持和B细胞记忆形成的关键机制。(C)2022 Elsevier Inc.版权所有。
The transcription factor Bach2 serves as a crucial regulator of the germinal center (GC) reaction, which is required for production of high-affinity antibodies and establishment of long-lived B cell memory. However, the stage at which Bach2 controls the GC programs and the precise mechanism underlying these processes remain poorly understood. In this study, we show that genetic ablation of Bach2 in GC B cells of mice impairs their survival and maintenance, and memory B cell formation. These defects can be rescued by enforced expression of anti-apoptotic gene Bcl2. As expected, Bach2-deficient GC B cells are defective in antibody affinity maturation, but have normal somatic hyper mutation and class switch recombination of immunoglobulin genes. Mechanistically, Bach2 controls the GC programs by directly repressing pro-apoptotic gene Bim and a set of genes involved in cell stress response and metabolic processes. Thus, our work reveals the precise roles of Bach2 in the GC biology, and demonstrates that Bach2 acts as a crucial survival regulator of GC B cells, providing a key mechanism underlying GC B maintenance and B cell memory formation.(c) 2022 Elsevier Inc. All rights reserved.