The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help.
The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help.
复制标题
DOI：
10.1084/jem.20161263
复制
发表时间：
2017-04-03
期刊：
影响因子：
--
通讯作者：
Kurosaki T
中科院分区：
文献类型：
--
作者：
Inoue T;Shinnakasu R;Ise W;Kawai C;Egawa T;Kurosaki T
Inoue等表明Foxo 1不仅控制GC极化，而且控制GC B细胞增殖，后者由Foxo 1依赖性BATF上调介导。生殖中心（GC）B细胞在两种状态之间循环，亮区（LZ）和暗区（DZ），并且在后者中，它们增殖并使它们的免疫球蛋白基因超突变。这种功能转变是如何发生的仍然存在争议。在这项研究中，我们证明，切除Foxo 1后，GC的发展导致的DZ GC B细胞的损失和破坏的GC架构，这是符合最近的研究。从机制上讲，即使在提供足够的T细胞帮助下，Foxo 1缺陷型GC B细胞的增殖扩增也比对照组少。此外，我们发现转录因子BATF在LZ GC B细胞中以Foxo 1依赖的方式被瞬时诱导，并且BATF的缺失类似地导致GC破坏。因此，我们的研究结果与一个模型是一致的，其中从LZ到DZ的开关是在接受T细胞帮助后触发的，并表明Foxo1介导的BATF上调至少部分参与了这一开关。
Inoue et al. show that Foxo1 controls not only GC polarization but also GC B cell proliferation, the latter of which is mediated by Foxo1-dependent BATF up-regulation. Germinal center (GC) B cells cycle between two states, the light zone (LZ) and the dark zone (DZ), and in the latter they proliferate and hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In this study, we demonstrate that ablation of Foxo1 after GC development led to the loss of the DZ GC B cells and disruption of the GC architecture, which is consistent with recent studies. Mechanistically, even upon provision of adequate T cell help, Foxo1-deficient GC B cells showed less proliferative expansion than controls. Moreover, we found that the transcription factor BATF was transiently induced in LZ GC B cells in a Foxo1-dependent manner and that deletion of BATF similarly led to GC disruption. Thus, our results are consistent with a model where the switch from the LZ to the DZ is triggered after receipt of T cell help, and suggest that Foxo1-mediated BATF up-regulation is at least partly involved in this switch.