Identification of a New Subset of Lymph Node Stromal Cells Involved in Regulating Plasma Cell Homeostasis

Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):E6826-E6835. doi: 10.1073/pnas.1712628115. Epub 2018 Jul 2.

Abstract

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

Keywords: FRC subsets; extrafollicular B cell differentiation; humoral response; lymph node medulla; plasma cell survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation*
  • B-Cell Activating Factor / immunology
  • Chemokine CXCL12 / immunology
  • Homeostasis / immunology*
  • Interleukin-6 / immunology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology*
  • Male
  • Mice
  • Plasma Cells / cytology
  • Plasma Cells / immunology*
  • Stromal Cells / cytology
  • Stromal Cells / immunology

Substances

  • B-Cell Activating Factor
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Interleukin-6
  • Tnfsf13b protein, mouse
  • interleukin-6, mouse