B cell-mediated antigen presentation is required for the pathogenesis of acute cardiac allograft rejection.
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.
Noorchashm
Hooman
H
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
Reed
Amy J
AJ
Rostami
Susan Y
SY
Mozaffari
Raha
R
Zekavat
Ghazal
G
Koeberlein
Brigitte
B
Caton
Andrew J
AJ
Naji
Ali
A
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
D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D007519:Isoantigens