B Cell Biology Lab, Vascular Pathophysiology Area, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Cellomics Unit, Cell &Developmental Biology Area, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Nat Commun. 2017 Jul 5;8:16067. doi: 10.1038/ncomms16067.
In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional programme, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of PC differentiation. Restoration of Blimp-1 levels partially rescues the proliferation defect of CTCF-deficient B cells. Thus, our data reveal an essential function of CTCF in maintaining the GC transcriptional programme and preventing premature PC differentiation.
在生发中心（GC）中，成熟 B 细胞在分化为记忆 B 细胞或长寿浆细胞（PC）之前经历强烈的增殖和免疫球蛋白基因修饰。GC B 细胞到 PC 的转变涉及主要的转录开关，促进细胞增殖停止和分泌免疫球蛋白的产生。在这里，我们表明 CCCTC 结合因子（CTCF）是体内 GC 反应所必需的，而体外 CTCF 的需求并非普遍存在，而是取决于用于 B 细胞激活的途径。CTCF 维持 GC 转录程序，允许高增殖率，并抑制 PC 分化的主调控因子 Blimp-1 的表达。恢复 Blimp-1 水平部分挽救了 CTCF 缺陷 B 细胞的增殖缺陷。因此，我们的数据揭示了 CTCF 在维持 GC 转录程序和防止过早 PC 分化方面的重要功能。
