title: T Cell Production of IFNγ in Response to TLR7/IL-12 Stimulates Optimal B Cell Responses to Viruses.
abstract: Knowledge of the processes that underlie IgG subclass switching could inform strategies designed to counteract infections and autoimmunity. Here we show that TLR7 ligands induce subsets of memory CD4 and CD8 T cells to secrete interferon γ (IFNγ) in the absence of antigen receptor stimulation. In turn, TLR ligation and IFNγ cause B cells to express the transcription factor, T-bet, and to switch immunoglobulin production to IgG2a/c. Absence of TLR7 in T cells leads to the impaired T-bet expression in B cells and subsequent inefficient IgG2a isotype switching both in vitro and during the infection with Friend virus in vivo. Our results reveal a surprising mechanism of antiviral IgG subclass switching through T-cell intrinsic TLR7/IL-12 signaling.
authors.affiliation: Howard Hughes Medical Institute, Denver, Colorado, 80206, United States of America.|Department of Biomedical Sciences, National Jewish Health and Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80206, United States of America.
authors.forename: Kira
authors.initials: K
authors.lastname: Rubtsova
authors.affiliation: Howard Hughes Medical Institute, Denver, Colorado, 80206, United States of America.|Department of Biomedical Sciences, National Jewish Health and Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80206, United States of America.
authors.forename: Anatoly V
authors.initials: AV
authors.lastname: Rubtsov
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado 80045, United States of America.|Department of Immunology and Microbiology, University of Colorado Denver, Aurora, Colorado 80045, United States of America.
authors.forename: Kalani
authors.initials: K
authors.lastname: Halemano
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado 80045, United States of America.|Department of Immunology and Microbiology, University of Colorado Denver, Aurora, Colorado 80045, United States of America.
authors.forename: Sam X
authors.initials: SX
authors.lastname: Li
authors.affiliation: Howard Hughes Medical Institute, Denver, Colorado, 80206, United States of America.|Department of Biomedical Sciences, National Jewish Health and Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80206, United States of America.|Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, United States of America.|Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Aurora, Colorado 80045, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado 80045, United States of America.|Department of Immunology and Microbiology, University of Colorado Denver, Aurora, Colorado 80045, United States of America.
authors.forename: Mario L
authors.initials: ML
authors.lastname: Santiago
authors.affiliation: Howard Hughes Medical Institute, Denver, Colorado, 80206, United States of America.|Department of Biomedical Sciences, National Jewish Health and Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80206, United States of America.|University of Colorado School of Medicine, Aurora, Colorado 80045, United States of America.|Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Aurora, Colorado 80045, United States of America.
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005622:Friend murine leukemia virus / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D007074:Immunoglobulin G; D053594:Myeloid Differentiation Factor 88; D051199:Toll-Like Receptor 7; D018664:Interleukin-12; D007371:Interferon-gamma; C402365:resiquimod