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J Exp Med. 2018 Apr 2;215(4):1227-1243. doi: 10.1084/jem.20160832. Epub 2018 Mar 16.

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

Author information

1
Institute of Immunology and Immunotherapy, Medical School/IBR, University of Birmingham, Birmingham, England, UK.
2
Deutsches Rheuma-Forschungszentrum Berlin, a Leibniz Institute, Berlin, Germany.
3
Division of Genetics, Department of Biology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
4
Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX.
5
Translational Innovation Platform, Immunology, Merck KGaA, Darmstadt, Germany.
6
Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, London, England, UK.
7
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
8
Charité Universitätsmedizin, Berlin, Germany.
9
Institute of Immunology and Immunotherapy, Medical School/IBR, University of Birmingham, Birmingham, England, UK K.M.Toellner@bham.ac.uk.

Abstract

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.

PMID:
29549115
PMCID:
PMC5881458
DOI:
10.1084/jem.20160832
[Indexed for MEDLINE]
Free PMC Article

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