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

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+ 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism
  • Cell Differentiation
  • Cell Movement
  • Chemokines / metabolism
  • Gene Expression Regulation
  • Germinal Center / cytology*
  • Immunity
  • Interferon Regulatory Factors / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism
  • Ligands
  • Lymphocyte Activation / immunology
  • Mice, Inbred C57BL
  • Plasma Cells / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction*
  • Stromal Cells / cytology*
  • Stromal Cells / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Transmembrane Activator and CAML Interactor Protein / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism


  • Antigens
  • Chemokines
  • Interferon Regulatory Factors
  • Interleukins
  • Ligands
  • RNA, Messenger
  • Tnfsf13 protein, mouse
  • Transmembrane Activator and CAML Interactor Protein
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • interferon regulatory factor-4
  • interleukin-21