The role of B cells in solid organ transplantation

The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.

► Growing evidence shows that following solid organ transplantation, alloantibody leads to progressive graft injury and loss. ► Control of T cell-mediated acute rejection does not necessarily avoid B cell activation and alloantibody. ► We have developed a murine and a non-human primate model for progressive antibody-mediated rejection that in many ways mimic late antibody-mediated rejection in humans. ► Some of the historical aspects of B cell immunity in transplantation are reviewed, and we outline our current thinking about the role of B cells in organ transplantation.