title: B cell homeostasis and follicle confines are governed by fibroblastic reticular cells.
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.
authors.affiliation: 1] Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA. [2].
authors.forename: Viviana
authors.initials: V
authors.lastname: Cremasco
authors.affiliation: 1] Program in Cellular and Molecular Medicine, Children's Hospital, Boston, Massachusetts, USA. [2] Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA. [3].
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Woodruff
authors.affiliation: Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Onder
authors.affiliation: Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.
authors.forename: Jovana
authors.initials: J
authors.lastname: Cupovic
authors.affiliation: Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Nieves-Bonilla
authors.affiliation: Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Schildberg
authors.affiliation: 1] Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA. [2] Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chang
authors.affiliation: 1] Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Pharmacology, University of Milan, Milan, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Cremasco
authors.affiliation: Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Harvey
authors.affiliation: Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wucherpfennig
authors.affiliation: Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.affiliation: 1] Program in Cellular and Molecular Medicine, Children's Hospital, Boston, Massachusetts, USA. [2] Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.affiliation: 1] Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA. [3].
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Turley
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D008164:Luminescent Proteins; C505720:Tnfsf13b protein, mouse