Department of Medicine, Section of Rheumatology, and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL, USA.
Department of Medicine, Section of Rheumatology, and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL, USA.
Trends Immunol. 2023 Sep;44(9):668-677. doi: 10.1016/j.it.2023.06.010. Epub 2023 Aug 10.
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.
在哺乳动物中，B 细胞在骨髓内发育时严格将增殖与体细胞突变分隔开来，然后在外周的生发中心 (GC) 中成熟。如果不能这样做，就会有自身免疫和肿瘤转化的风险。最近的研究描述了 B 细胞前体细胞如何通过细胞因子信号通路、表观遗传染色质调控以及 3D 染色质构象的重塑，在增殖和突变之间转换。我们提出了一个 GC 的三区模型，描述了增殖和突变是如何被调控的。利用这个模型，我们考虑了 B 细胞前体细胞中的最近的机制发现如何为 GC B 细胞功能模型提供信息，并揭示了体液免疫、自身免疫和淋巴瘤发生的基本机制。
