title: An obligatory role for lung infiltrating B cells in the immunopathogenesis of obliterative airway disease induced by antibodies to MHC class I molecules.
abstract: Using a murine model, we demonstrated that endobronchial administration of antibodies (Abs) to major histocompatibility complex (MHC) class I results in cellular infiltration, epithelial metaplasia, fibrosis and obstruction of the small airways (obliterative airway disease [OAD]) mediated predominantly by Th17 responses to self-antigens. This resembles bronchiolitis obliterans syndrome developed following human lung transplantation. Since B cells play a crucial role in induction of autoimmune responses, we defined the role of B cells and its antigen presenting properties in induction of OAD in this study. Anti-MHC class I was administered endobronchially in B(-/-)  and wild-type mice. In contrast to wild type, B(-/-)  animals did not demonstrate cellular infiltration, epithelial metaplasia and obstruction of airways following anti-MHC. Frequency of K-α1 tubulin and CollagenV-specific IL-17 cells was significantly decreased in B(-/-)  mice. As expected, Abs against self-antigens and germinal center formation were not developed in B(-/-)  mice. Thus, we conclude that B cells and its antigen presenting capacity play an important role in induction of immune responses to self-antigens and immunopathogenesis of OAD following the administration of anti-MHC. Therefore, strategies to block B-cell and its antigen presenting functions should be considered for preventing the development of chronic rejection.
authors.affiliation: Departments of SurgeryPathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: N
authors.initials: N
authors.lastname: Fukami
authors.forename: S
authors.initials: S
authors.lastname: Ramachandran
authors.forename: M
authors.initials: M
authors.lastname: Takenaka
authors.forename: J
authors.initials: J
authors.lastname: Weber
authors.forename: V
authors.initials: V
authors.lastname: Subramanian
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000473:pathology*; D005355:Fibrosis / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001324:Autoantigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D020381:Interleukin-17