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

摘要

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 CD157~(high)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~(+)CD157~(high)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. Graphical Abstract.