Institute of Immunology and Immunotherapy, Medical School/IBR, University of Birmingham, Birmingham, England, UK.
Deutsches Rheuma-Forschungszentrum Berlin, a Leibniz Institute, Berlin, Germany.
J Exp Med. 2018 Apr 2;215(4):1227-1243. doi: 10.1084/jem.20160832. Epub 2018 Mar 16.
Germinal centers (GCs) are the sites where B cells undergo affinity maturation. The regulation of cellular output from the GC is not well understood. Here, we show that from the earliest stages of the GC response, plasmablasts emerge at the GC-T zone interface (GTI). We define two main factors that regulate this process: Tfh-derived IL-21, which supports production of plasmablasts from the GC, and TNFSF13 (APRIL), which is produced by a population of podoplanin CD157 fibroblastic reticular cells located in the GTI that are also rich in message for IL-6 and chemokines CXCL12, CCL19, and CCL21. Plasmablasts in the GTI express the APRIL receptor TNFRSF13B (TACI), and blocking TACI interactions specifically reduces the numbers of plasmablasts appearing in the GTI. Plasma cells generated in the GTI may provide an early source of affinity-matured antibodies that may neutralize pathogens or provide feedback regulating GC B cell selection.
生发中心（GCs）是 B 细胞发生亲和力成熟的部位。GC 中细胞输出的调节机制尚不清楚。在这里，我们发现从 GC 反应的最早阶段开始，浆母细胞就在 GC-T 区界面（GTI）出现。我们定义了两个主要调节此过程的因素：Tfh 细胞衍生的 IL-21，它支持 GC 中浆母细胞的产生；以及 TNFSF13（APRIL），它由位于 GTI 中的一群富含 IL-6 和趋化因子 CXCL12、CCL19 和 CCL21 信息的 podoplanin CD157 成纤维细胞网状细胞产生。GTI 中的浆母细胞表达 APRIL 受体 TNFRSF13B（TACI），而阻断 TACI 相互作用会特异性减少出现在 GTI 中的浆母细胞数量。在 GTI 中产生的浆细胞可能为亲和力成熟的抗体提供早期来源，这些抗体可能中和病原体或提供反馈调节 GC B 细胞选择。
