title: B cell-mediated antigen presentation is required for the pathogenesis of acute cardiac allograft rejection.
abstract: Acute allograft rejection requires the activation of alloreactive CD4 T cells. Despite the capacity of B cells to act as potent APCs capable of activating CD4 T cells in vivo, their role in the progression of acute allograft rejection was unclear. To determine the contribution of B cell APC function in alloimmunity, we engineered mice with a targeted deficiency of MHC class II-mediated Ag presentation confined to the B cell compartment. Cardiac allograft survival was markedly prolonged in these mice as compared to control counterparts (median survival time, >70 vs 9.5 days). Mechanistically, deficient B cell-mediated Ag presentation disrupted both alloantibody production and the progression of CD4 T cell activation following heart transplantation. These findings demonstrate that indirect alloantigen presentation by recipients' B cells plays an important role in the efficient progression of acute vascularized allograft rejection.
authors.affiliation: Harrison Department of Surgical Research, and Department of Surgery, University of Pennsylvania Medical Center, 4 Silverstein Pavilion, 3400 Spruce Street, Philadelphia, PA 19104, USA. Hooman.Noorchashm@uphs.upenn.edu
authors.forename: Hooman
authors.initials: H
authors.lastname: Noorchashm
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Reed
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Rostami
authors.forename: Raha
authors.initials: R
authors.lastname: Mozaffari
authors.forename: Ghazal
authors.initials: G
authors.lastname: Zekavat
authors.forename: Brigitte
authors.initials: B
authors.lastname: Koeberlein
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018183:Transplantation Chimera
chemical_list: D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D007519:Isoantigens