Germinal centers (GCs) are confined anatomic regions where rapidly proliferating B cells undergo somatic mutation and selection and eventual differentiation into memory B cells or long‐lived plasma cells. GCs are also the origin of malignancy, namely follicular lymphoma (FL), GC B cell‐diffuse large B cell lymphoma (GCB‐DLBCL), and Burkitt lymphoma (BL). GC B cell lymphomas maintain their GC transcriptional signatures and sustain many features of the GC microenvironment, including CD4⁺ T follicular helper (Tfh) cells. Tfh cells are essential for the formation and maintenance of GCs, providing critical helper signals such as CD40L. Large‐scale sequencing efforts have led to new insights about the tightly regulated selection mechanisms that are commonly targeted during GC B cell lymphomagenesis. For instance, HVEM, a frequently mutated surface molecule in GC‐derived lymphomas, engages the inhibitory receptor BTLA on Tfh cells and loss of HVEM leads to exaggerated T cell help. Here, we review current understanding of how Tfh cells contribute to the selection of GC B cells, with a particular emphasis on how Tfh cell signals may contribute to lymphomagenesis. The possibility of targeting Tfh cells for the treatment of GC‐derived lymphomas is discussed.

中文翻译：

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滤泡辅助 T 细胞在生发中心 B 细胞选择和淋巴瘤发生中的作用。


生发中心 (GC) 是一个有限的解剖区域，其中快速增殖的 B 细胞经历体细胞突变和选择，并最终分化为记忆 B 细胞或长寿命浆细胞。 GC也是恶性肿瘤的起源，即滤泡性淋巴瘤（FL）、GC B细胞弥漫性大B细胞淋巴瘤（GCB-DLBCL）和伯基特淋巴瘤（BL）。 GC B 细胞淋巴瘤维持其 GC 转录特征并维持 GC 微环境的许多特征，包括 CD4 ⁺ T 滤泡辅助 (Tfh) 细胞。 Tfh 细胞对于 GC 的形成和维持至关重要，可提供关键的辅助信号，例如 CD40L。大规模测序工作带来了关于 GC B 细胞淋巴瘤发生过程中通常针对的严格调控选择机制的新见解。例如，HVEM 是 GC 衍生淋巴瘤中一种经常突变的表面分子，它与 Tfh 细胞上的抑制性受体 BTLA 结合，HVEM 的缺失会导致 T 细胞的帮助过度。在这里，我们回顾了目前对 Tfh 细胞如何促进 GC B 细胞选择的理解，特别强调 Tfh 细胞信号如何促进淋巴瘤发生。讨论了靶向 Tfh 细胞治疗 GC 衍生淋巴瘤的可能性。