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

N. Fukami, S. Ramachandran, M. Takenaka, J. Weber, V. Subramanian, T. Mohanakumar

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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-α 1 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.

Original languageEnglish
Pages (from-to)867-876
Number of pages10
JournalAmerican Journal of Transplantation
Volume12
Issue number4
DOIs
Publication statusPublished - 04-2012

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'An obligatory role for lung infiltrating B cells in the immunopathogenesis of obliterative airway disease induced by antibodies to MHC class I molecules'. Together they form a unique fingerprint.

Cite this