title: Contribution of B cells and antibody to cardiac allograft vasculopathy.
abstract: BACKGROUND
  The aim of this study was to determine the role of alloantibody in the development of cardiac allograft vasculopathy (AV). AV is the main pathologic indicator of chronic cardiac graft rejection resulting in graft loss at 10 years posttransplant. In AV, a neointimal lesion forms resulting in luminal occlusion and damage to the transplanted organ. AV is T-cell mediated, but the role played by B cells and antibody in AV development has been controversial. No studies have been conducted in the presence of a clinically relevant immunosuppressant. In our study, we use cyclosporin A, a calcineurin inhibitor.
  
  
  METHODS
  Two models of B-cell deficiency were used as recipients of a C3H/HeJ abdominal aortic graft; grafts were harvested at 8 weeks. T- and B-cell immunodeficient mice (RAG1-/-) received passively transferred anti-C3H antibody, raised in B6 mice. Cyclosporin A was administered daily to both control and experimental groups. Alpha-actin staining was used to identify myofibroblasts in the neointima.
  
  
  RESULTS
  Lesions in B-cell-deficient B6 mice were not significantly different in size from those of control mice. Lesions in both B-cell-deficient and wild-type mice showed similar levels of alpha-actin positivity. Passive transfer of antibody to RAG1-/- mice resulted in small, alpha-actin-positive lesions.
  
  
  CONCLUSIONS
  B cells are not required for the development of AV, but the presence of an alloantibody can contribute to AV. We hypothesize that the alloantibody mediates AV by initiating complement-mediated killing of smooth muscle cells, based on an in vitro work. Of interest, we found that the neointimal lesions of B-cell-deficient mice and mice that received antibody showed the presence of alpha-actin in myofibroblasts.
authors.affiliation: Department of Surgery, Atlantic Centre for Transplantation Research, Microbiology and Immunology and Pathology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Alison
authors.initials: A
authors.lastname: Gareau
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Hirsch
authors.forename: Tim D G
authors.initials: TD
authors.lastname: Lee
authors.forename: Bjorn
authors.initials: B
authors.lastname: Nashan
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001012:Aorta, Abdominal / Q000637:transplantation; D001402:B-Lymphocytes / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007518:Isoantibodies / Q000378:metabolism*; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology
chemical_list: D000199:Actins; D018398:Homeodomain Proteins; D007166:Immunosuppressive Agents; D007518:Isoantibodies; C064658:RAG-1 protein; D016572:Cyclosporine