title: T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow.
abstract: Long-lived plasma cells (PCs) in the bone marrow (BM) are a critical source of antibodies after infection or vaccination, but questions remain about the factors that control PCs. We found that systemic infection alters the BM, greatly reducing PCs and regulatory T (Treg) cells, a population that contributes to immune privilege in the BM. The use of intravital imaging revealed that BM Treg cells display a distinct behavior characterized by sustained co-localization with PCs and CD11c-YFP+cells. Gene expression profiling indicated that BM Treg cells express high levels of Treg effector molecules, and CTLA-4 deletion in these cells resulted in elevated PCs. Furthermore, preservation of Treg cells during systemic infection prevents PC loss, while Treg cell depletion in uninfected mice reduced PC populations. These studies suggest a role for Treg cells in PC biology and provide a potential target for the modulation of PCs during vaccine-induced humoral responses or autoimmunity.
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Arielle
authors.initials: A
authors.lastname: Glatman Zaretsky
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Konradt
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Fabien
authors.initials: F
authors.lastname: Dépis
authors.affiliation: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
authors.forename: James B
authors.initials: JB
authors.lastname: Wing
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Radhika
authors.initials: R
authors.lastname: Goenka
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Daniela Gomez
authors.initials: DG
authors.lastname: Atria
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Silver
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Sunglim
authors.initials: S
authors.lastname: Cho
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Amaya I
authors.initials: AI
authors.lastname: Wolf
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Quinn
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Julie B
authors.initials: JB
authors.lastname: Engiles
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Brown
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Beiting
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Erikson
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: David
authors.initials: D
authors.lastname: Allman
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
authors.affiliation: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Li-Fan
authors.initials: LF
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christophe O
authors.initials: CO
authors.lastname: Benoist
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: chunter@vet.upenn.edu.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000276:immunology; D056724:Immunity, Humoral; D016130:Immunophenotyping / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D060908:CTLA-4 Antigen
keywords: B cells; T regulatory cell; antibody; bone marrow; infectious disease; plasma cell