Plasma cell output from germinal centers is regulated by signals from Tfh and stromal cells.

Plasma cell output from germinal centers is regulated by signals from Tfh and stromal cells.
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DOI:
10.1084/jem.20160832
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发表时间:
2018-04-02
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Toellner KM
Toellner KM
中科院分区:
其他
文献类型:
--
作者:
Zhang Y;Tech L;George LA;Acs A;Durrett RE;Hess H;Walker LSK;Tarlinton DM;Fletcher AL;Hauser AE;Toellner KM

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在生发中心(GC)中产生的浆母细胞出现在GC-T区界面(GTI)。Zhang等证明了这一过程的两个主要调节因子:Tfh衍生的IL-21和由位于GTI中的CD 157高成纤维网状细胞产生的APRIL。生殖中心(GC)是B细胞经历亲和力成熟的位点。GC对细胞输出的调节还不清楚。在这里,我们表明,从GC反应的最早阶段,浆母细胞出现在GC-T区界面(GTI)。我们定义了两个调节这一过程的主要因子:Tfh衍生的IL-21,其支持GC产生浆母细胞; TNFSF 13(APRIL),其由位于GTI的podoplanin+ CD 157高成纤维细胞网状细胞群产生,这些细胞也富含IL-6和趋化因子CXCL 12、CCL 19和CCL 21的信息。GTI中的浆母细胞表达APRIL受体TNFRSF 13 B(TACI),阻断TACI相互作用特异性地减少GTI中出现的浆母细胞的数量。GTI中产生的浆细胞可以提供亲和力成熟抗体的早期来源,这些抗体可以中和病原体或提供调节GC B细胞选择的反馈。
Plasmablasts generated in germinal centers (GC) emerge at the GC–T zone interface (GTI). Zhang et al. demonstrate two major regulators of this process: Tfh-derived IL-21 and APRIL produced by CD157high fibroblastic reticular cells located in the GTI. 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+ CD157high 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.
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