title: Innate immune signals modulate antiviral and polyreactive antibody responses during severe respiratory syncytial virus infection.
abstract: Antiviral antibody production during respiratory syncytial virus (RSV) infection in infants is poorly understood. To characterize local B lymphocyte responses, lung tissue and secretions from infants with RSV bronchiolitis were analyzed for innate B cell-stimulating factors and antiviral antibodies. In lung tissues of infants with fatal RSV bronchiolitis, CD20(+) lymphocytes and IgM-positive, IgG-positive, and IgA-positive plasma cells were prominent but CD4(+) T lymphocytes were not. Type I interferon-induced proteins and B cell tropic factors, including B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), were colocalized in infected epithelium. In nasopharyngeal secretions from infants who survived RSV infection, class-switched antiviral and antinucleosomal antibodies were detected at presentation and correlated with BAFF and APRIL levels. Expression of APRIL and antiviral antibodies of IgA and IgM but not IgG isotype predicted better oxygen saturation. We conclude that B lymphocyte-stimulating factors derived from infected epithelium are primary determinants of the mucosal antibody response in infant RSV bronchiolitis.
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA. jennifer.reed@fda.hhs.gov
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Reed
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Welliver
authors.forename: Gary P
authors.initials: GP
authors.lastname: Sims
authors.forename: Luann
authors.initials: L
authors.lastname: McKinney
authors.forename: Luis
authors.initials: L
authors.lastname: Velozo
authors.forename: Luis
authors.initials: L
authors.lastname: Avendano
authors.forename: Karen
authors.initials: K
authors.lastname: Hintz
authors.forename: Jayson
authors.initials: J
authors.lastname: Luma
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welliver
mesh_terms: D000914:Antibodies, Viral / Q000097:blood* / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood / Q000378:metabolism; D007223:Infant; D008168:Lung / Q000276:immunology / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D000914:Antibodies, Viral; D007136:Immunoglobulins; D010100:Oxygen