Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation

Xiaohu Fan, Andrew Ang, Stacey M. Pollock-BarZiv, Anne I. Dipchand, Phillip Ruiz, Gregory Wilson, Jeffrey L. Platt, Lori J. West

Research output: Contribution to journalArticle

164 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1227-1233
Number of pages7
JournalNature medicine
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2004

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Fan, X., Ang, A., Pollock-BarZiv, S. M., Dipchand, A. I., Ruiz, P., Wilson, G., Platt, J. L., & West, L. J. (2004). Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation. Nature medicine, 10(11), 1227-1233. https://doi.org/10.1038/nm1126