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

Nature Immunology volume 15, pages 973981 (2014) | Download Citation

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.

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Acknowledgements

We thank L. Cameron for technical assistance at the Dana-Farber cancer Institute Confocal Imaging core. Supported by the US National Institutes of Health (5R01 DK074500-08, 2P01AI045757-15, R21 CA182598-01 to S.J.T.; R01 AI039246, P01 AI078897 and R37 AI054636 to M.C.C.; and T32 CA 070083-15 to V.C.), the Barr Foundation (S.J.T.), the Cancer Research Institute (V.C.), the Vontobel Foundation (to B.L.) and the Helmut Horten Foundation (to B.L.).

Author information

Author notes

    • Shannon J Turley

    Present address: Genentech, South San Francisco, California, USA.

    • Viviana Cremasco
    •  & Matthew C Woodruff

    These authors contributed equally to this work.

Affiliations

  1. Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA.

    • Viviana Cremasco
    • , Janice M Nieves-Bonilla
    • , Frank A Schildberg
    • , Jonathan Chang
    • , Floriana Cremasco
    • , Christopher J Harvey
    • , Kai Wucherpfennig
    •  & Shannon J Turley
  2. Program in Cellular and Molecular Medicine, Children's Hospital, Boston, Massachusetts, USA.

    • Matthew C Woodruff
    •  & Michael C Carroll
  3. Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA.

    • Matthew C Woodruff
    •  & Jonathan Chang
  4. Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.

    • Lucas Onder
    • , Jovana Cupovic
    •  & Burkhard Ludewig
  5. Department of Pharmacology, University of Milan, Milan, Italy.

    • Floriana Cremasco
  6. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

    • Michael C Carroll
  7. Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

    • Shannon J Turley

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Contributions

V.C. and M.C.W. designed and performed experiments and analyzed results; L.O., J.Cu., J.M.N.-B., F.A.S., J.Ch., F.C. and C.J.H. performed experiments; K.W. provided reagents and critical input on the manuscript; B.L. provided Ccl19-Cre mice and critical input on the manuscript; M.C.C. and S.J.T. designed and supervised the study; and V.C. and S.J.T. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Michael C Carroll or Shannon J Turley.

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DOI

https://doi.org/10.1038/ni.2965

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