Although over 50 years have passed since its first laboratory description, intentional induction of immune tolerance to foreign antigens has remained an elusive clinical goal. We previously reported that the requirement for ABO compatibility in heart transplantation is not applicable to infants. Here, we show that ABO-incompatible heart transplantation during infancy results in development of B-cell tolerance to donor blood group A and B antigens. This mimics animal models of neonatal tolerance and indicates that the human infant is susceptible to intentional tolerance induction. Tolerance in this setting occurs by elimination of donor-reactive B lymphocytes and may be dependent upon persistence of some degree of antigen expression. These findings suggest that intentional exposure to nonself A and B antigens may prolong the window of opportunity for ABO-incompatible transplantation, and have profound implications for clinical research on tolerance induction to T-independent antigens relevant to xenotransplantation.
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We thank K. Wood and M. Sykes for discussion and advice, and P. Morris and R. Zhong for reading of our manuscript. This work was supported with funding from the Canadian Institutes for Health Research, the Heart and Stroke Foundation of Ontario, and the Research Training Competition at The Hospital for Sick Children.
The authors declare no competing financial interests.
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Fan, X., Ang, A., Pollock-BarZiv, S. et al. Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation. Nat Med 10, 1227–1233 (2004). https://doi.org/10.1038/nm1126
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