Identification of a new subset of lymph node stromal cells involved in regulating plasma cell homeostasis

Research output: Contribution to journalArticle

Authors

  • Hsin-Ying Huang
  • Ana Rivas-Caicedo
  • François Renevey
  • Hélène Cannelle
  • Elisa Peranzoni
  • Leonardo Scarpellino
  • Arnaud Pommier
  • Karin Schaeuble
  • Stéphanie Favre
  • Tobias K. Vogt
  • Fernando Arenzana-Seisdedos
  • Pascal Schneider
  • Emmanuel Donnadieu
  • Sanjiv A. Luther

Colleges, School and Institutes

External organisations

  • University of Lausanne
  • Paris Descartes University
  • Institut Pasteur

Abstract

Antibody-secreting plasma cells (PC) arise rapidly during adaptive immunity to control infections. The early PC are retained within the reactive lymphoid organ where their localization and homeostasis relies on extrinsic factors, presumably produced by local niche cells. While myeloid cells have been proposed to form those niches, the contribution by co-localizing stromal cells has remained unclear. Here, we characterized a subset of fibroblastic reticular cells (FRC) that forms a dense meshwork throughout medullary cords of lymph nodes (LN) where PC reside. This medullary FRC type is shown to be anatomically, phenotypically and functionally distinct from T zone FRC, both in mice and humans. By using static and dynamic imaging approaches, we provide evidence that medullary FRC are the main cell type in contact with PC guiding them in their migration. Medullary FRC also represent a major local source of the PC survival factors IL-6, BAFF and CXCL12, besides producing also APRIL. In vitro, medullary FRC alone or in combination with macrophages promote PC survival while other LN cell types do not have this property. Thus, we propose that this new FRC subset, together with medullary macrophages, forms PC survival niches within the LN medulla, and thereby helps promoting the rapid development of humoral immunity which is critical in limiting early pathogen spread.

Details

Original languageEnglish
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Early online date2 Jul 2018
Publication statusE-pub ahead of print - 2 Jul 2018

Keywords

  • FRC subsets , lymph node medulla, extrafollicular B cell differentiation , plasma cell survival, humoral response