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

Autor:	Zhang Y; Institute of Immunology and Immunotherapy, Medical School/IBR, University of Birmingham, Birmingham, England, UK., Tech L; Deutsches Rheuma-Forschungszentrum Berlin, a Leibniz Institute, Berlin, Germany., George LA; Institute of Immunology and Immunotherapy, Medical School/IBR, University of Birmingham, Birmingham, England, UK., Acs A; Division of Genetics, Department of Biology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Durrett RE; Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX., Hess H; Translational Innovation Platform, Immunology, Merck KGaA, Darmstadt, Germany., Walker LSK; Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, London, England, UK., Tarlinton DM; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia., Fletcher AL; Institute of Immunology and Immunotherapy, Medical School/IBR, University of Birmingham, Birmingham, England, UK., Hauser AE; Deutsches Rheuma-Forschungszentrum Berlin, a Leibniz Institute, Berlin, Germany.; Charité Universitätsmedizin, Berlin, Germany., Toellner KM; Institute of Immunology and Immunotherapy, Medical School/IBR, University of Birmingham, Birmingham, England, UK K.M.Toellner@bham.ac.uk.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2018 Apr 02; Vol. 215 (4), pp. 1227-1243. Date of Electronic Publication: 2018 Mar 16.
DOI:	10.1084/jem.20160832
Abstrakt:	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. (© 2018 Zhang et al.)
Databáze:	MEDLINE
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