An obligatory role for lung infiltrating B cells in the immunopathogenesis of obliterative airway disease induced by antibodies to MHC class I molecules

Am J Transplant. 2012 Apr;12(4):867-76. doi: 10.1111/j.1600-6143.2011.03917.x. Epub 2012 Jan 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology*
  • Bronchiolitis Obliterans / etiology*
  • Bronchiolitis Obliterans / pathology*
  • Fibrosis / immunology
  • Flow Cytometry
  • Graft Rejection / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Immunoglobulin G / immunology*
  • Interleukin-17 / metabolism
  • Lung / immunology*
  • Lung / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / immunology


  • Autoantigens
  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Interleukin-17