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B Cell-Mediated Antigen Presentation Is Required for the Pathogenesis of Acute Cardiac Allograft Rejection¹

Harrison Department of Surgical Research, University of Pennsylvania Medical Center, Philadelphia, PA 19104

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants DK064603 and DK049814.

² H.N. and A.J.R. contributed equally to the design, execution, and preparation of this manuscript.

³ Address correspondence and reprint requests to Dr. Hooman Noorchashm, University of Pennsylvania Medical Center, Department of Surgery, 4 Silverstein Pavilion, 3400 Spruce Street, Philadelphia, PA 19104; E-mail address: Hooman.Noorchashm{at}uphs.upenn.edu or Dr. Ali Naji, University of Pennsylvania Medical Center, Department of Surgery, 4 Silverstein Pavilion, 3400 Spruce Street, Philadelphia, PA 19104; E-mail address: Ali.Naji{at}uphs.upenn.edu

⁴ Abbreviations used in this paper: DC, dendritic cell; BM, bone marrow; HA, hemagglutinin; int, intermediate; SEA, staphylococcal enterotoxin A; SP, single positive; Treg, T regulatory.