Department of Oto-Rhino-Laryngology, Ulm University Medical Center, Ulm, Germany.
Ulm University, Institute of Physiological Chemistry, Ulm, Germany.
Front Immunol. 2023 Feb 3;14:1125503. doi: 10.3389/fimmu.2023.1125503. eCollection 2023.
The germinal center (GC) reaction is a key process during an adaptive immune response to T cell specific antigens. GCs are specialized structures within secondary lymphoid organs, in which B cell proliferation, somatic hypermutation and antibody affinity maturation occur. As a result, high affinity antibody secreting plasma cells and memory B cells are generated. An effective GC response needs interaction between multiple cell types. Besides reticular cells and follicular dendritic cells, particularly B cells, T follicular helper (Tfh) cells as well as T follicular regulatory (Tfr) cells are a key player during the GC reaction. Whereas Tfh cells provide help to GC B cells in selection processes, Tfr cells, a specialized subset of regulatory T cells (Tregs), are able to suppress the GC reaction maintaining the balance between immune activation and tolerance. The formation and function of GCs is regulated by a complex network of signals and molecules at multiple levels. In this review, we highlight recent developments in GC biology by focusing on the transcriptional program regulating the GC reaction. This review focuses on the transcriptional co-activator BOB.1/OBF.1, whose important role for GC B, Tfh and Tfr cell differentiation became increasingly clear in recent years. Moreover, we outline how deregulation of the GC transcriptional program can drive lymphomagenesis.
生发中心（GC）反应是适应性免疫应答 T 细胞特异性抗原的关键过程。GC 是次级淋巴器官中的特化结构，其中发生 B 细胞增殖、体细胞超突变和抗体亲和力成熟。因此，产生了高亲和力的抗体分泌浆细胞和记忆 B 细胞。有效的 GC 反应需要多种细胞类型的相互作用。除了网状细胞和滤泡树突状细胞外，B 细胞、滤泡辅助性 T 细胞（Tfh）和滤泡调节性 T 细胞（Tfr）等 T 滤泡辅助细胞也是 GC 反应中的关键细胞。虽然 Tfh 细胞在选择过程中为 GC B 细胞提供帮助，但 Tfr 细胞是调节性 T 细胞（Tregs）的一个特殊亚群，能够抑制 GC 反应，维持免疫激活和耐受之间的平衡。GC 的形成和功能受多层次信号和分子的复杂网络调控。在这篇综述中，我们通过关注调节 GC 反应的转录程序，强调了 GC 生物学的最新进展。本综述重点介绍了转录共激活因子 BOB.1/OBF.1，近年来，其对 GC B、Tfh 和 Tfr 细胞分化的重要作用越来越明显。此外，我们概述了 GC 转录程序的失调如何驱动淋巴瘤的发生。
