B cell homeostasis and follicle confines are governed by fibroblastic reticular cells

Nat Immunol. 2014 Oct;15(10):973-81. doi: 10.1038/ni.2965. Epub 2014 Aug 24.

Abstract

Fibroblastic reticular cells (FRCs) are known to inhabit T cell-rich areas of lymphoid organs, where they function to facilitate interactions between T cells and dendritic cells. However, in vivo manipulation of FRCs has been limited by a dearth of genetic tools that target this lineage. Here, using a mouse model to conditionally ablate FRCs, we demonstrated their indispensable role in antiviral T cell responses. Unexpectedly, loss of FRCs also attenuated humoral immunity due to impaired B cell viability and follicular organization. Follicle-resident FRCs established a favorable niche for B lymphocytes via production of the cytokine BAFF. Thus, our study indicates that adaptive immunity requires an intact FRC network and identifies a subset of FRCs that control B cell homeostasis and follicle identity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Activating Factor / immunology
  • B-Cell Activating Factor / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Movement / immunology
  • Cell Survival / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Fibroblasts / immunology*
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Homeostasis / immunology*
  • Immunity, Humoral / immunology
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • B-Cell Activating Factor
  • Luminescent Proteins
  • Tnfsf13b protein, mouse