title: Cutting Edge: B Cell-Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection.
abstract: The role of Ab and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections, and T-bet promotes IgG2a isotype switching. However, whether IgG2a and B cell-expressed T-bet influence the host-pathogen balance during persisting infections is unclear. We demonstrate that B cell-specific loss of T-bet prevents control of persisting viral infection. T-bet in B cells controlled IgG2a production, as well as mucosal localization, proliferation, glycosylation, and a broad transcriptional program. T-bet controlled a broad antiviral program in addition to IgG2a because T-bet in B cells was important, even in the presence of virus-specific IgG2a. Our data support a model in which T-bet is a universal controller of antiviral immunity across multiple immune lineages.
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Burton E
authors.initials: BE
authors.lastname: Barnett
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Staupe
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Odorizzi
authors.affiliation: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Olesya
authors.identifier: 0000-0002-6271-0580
authors.initials: O
authors.lastname: Palko
authors.affiliation: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Vesselin T
authors.initials: VT
authors.lastname: Tomov
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;
authors.forename: Alison E
authors.initials: AE
authors.lastname: Mahan
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Gunn
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Diana
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Michael A
authors.initials: MA
authors.lastname: Paley
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032; and.
authors.forename: Steven L
authors.identifier: 0000-0002-1635-8619
authors.initials: SL
authors.lastname: Reiner
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Georg M
authors.identifier: 0000-0002-9792-4271
authors.initials: GM
authors.lastname: Lauer
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: John R
authors.initials: JR
authors.lastname: Teijaro
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; wherry@mail.med.upenn.edu.
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002908:Chronic Disease; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D020825:T-Box Domain Proteins / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D007074:Immunoglobulin G; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor