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Humoral immunity in xenotransplantation: B-cell tolerance and accommodation

Purpose of reviewImmunity poses the most daunting barrier to the clinical application of xenotransplantation. This barrier exists because xenografts carry many foreign antigens recognized by the innate and adaptive limbs of immunity and fail to incite regulatory processes that protect the graft. Although various agents and regimens have been developed to control immune responses, the difficulty of achieving control of immune responses to xenografts has stimulated interest in the application of tolerance or accommodation (resistance to immune-mediated injury) for improving survival and thus the clinical applicability of xenotransplantation. This review discusses recent advances in understanding and achieving tolerance and accommodation for xenotransplantation. Recent findingsAll xenografts are not equally susceptible to immune-mediated injury, and hence, tolerance and accommodation are not always needed. Cellular xenografts are susceptible to cellular rejection, which can be controlled by immunosuppression. Organ xenografts, on the other hand, are highly susceptible to humoral immunity and vascular disease that is not completely controlled by immunosuppression. Therefore, tolerance and accommodation may be needed for these transplants. SummaryHumoral immunity has seemed an unyielding obstacle to the success of organ xenotransplantation. Tolerance and accommodation could provide the tools to overcome this hurdle. This article reviews new insights and strategies for achieving tolerance and accommodation for xenotransplantation.