4.7 Article

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

Journal

NATURE IMMUNOLOGY
Volume 15, Issue 10, Pages 973-U222

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2965

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Funding

  1. US National Institutes of Health [5R01 DK074500-08, 2P01AI045757-15, R21 CA182598-01, R01 AI039246, P01 AI078897, R37 AI054636, T32 CA 070083-15]
  2. Barr Foundation
  3. Cancer Research Institute
  4. Vontobel Foundation
  5. Helmut Horten Foundation

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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.

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