在哺乳动物中，B细胞在骨髓中发育，然后通过边缘逐渐成熟的生发中心（GCs）严格将增殖与体细胞突变隔离。未能这样做会导致自身免疫和肿瘤转化的风险。最近的研究已经描述了B细胞祖细胞通过细胞因子信号传导通路、表观遗传染色质调控以及3D染色质构象的重构之间的增殖与突变转换。我们提出了一个描述增殖与突变调控的GC三区模型。利用这个模型，我们考虑了B细胞祖细胞最新的机制性发现如何为GC B细胞功能模型提供信息，并揭示了支持体液免疫、自身免疫和淋巴瘤发生的基本机制。版权所有©2023 Elsevier Ltd.

In mammals, B cells strictly segregate proliferation from somatic mutation as they develop within the bone marrow and then mature through germinal centers (GCs) in the periphery. Failure to do so risks autoimmunity and neoplastic transformation. Recent work has described how B cell progenitors transition between proliferation and mutation via cytokine signaling pathways, epigenetic chromatin regulation, and remodeling of 3D chromatin conformation. We propose a three-zone model of the GC that describes how proliferation and mutation are regulated. Using this model, we consider how recent mechanistic discoveries in B cell progenitors inform models of GC B cell function and reveal fundamental mechanisms underpinning humoral immunity, autoimmunity, and lymphomagenesis.Copyright © 2023 Elsevier Ltd. All rights reserved.