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

  title={Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation},
  author={Xiaohu Fan and A. L. Ang and Stacey M. Pollock-BarZiv and Anne I. Dipchand and Phillip Ruiz and Gregory John Wilson and Jeffrey L Platt and Lori J. West},
  journal={Nature Medicine},
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… 

Failure of Neonatal B-Cell Tolerance Induction by ABO-Incompatible Kidney Grafts in Piglets

Background ABO-incompatible (ABOi) infant heart transplantation results in B-cell tolerance to graft A/B antigens, confirming human susceptibility to acquired immunologic or “neonatal” tolerance as

Tolerance to incompatible ABO blood group antigens is not observed following homograft implantation.

ABO‐Compatible Retransplantation After ABO‐Incompatible Infant Heart Transplantation: Absence of Donor Specific Isohemagglutinins

  • S. KohlerR. Engmann R. Kozlik-Feldmann
  • Medicine
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2014
A case of an infant who underwent ABOi heart transplantation, with no evidence of DSI even 4 years after ABO‐compatible retransplantation is reported, suggesting the possibility of induced permanent B cell tolerance.

Development of B-cell memory in early childhood and the impact on antigen-specific tolerance after heart transplantation.

ABO-incompatible heart transplantation

Insight is provided into the clinical evolution of ABOi HTx and associated immunologic discoveries and current experiences and boundaries are discussed together with recent and potential future developments for utilization in other patient and age groups.

ABO-incompatible solid-organ transplantation.

The stage is set to eliminate ABO as a barrier to solid-organ transplantation.

B cell tolerance and xenotransplantation

This review summarizes recent advances in the understanding of B cell tolerance in rodent models and patients and describes strategies for tolerance induction developed in the animal models that may be applied clinically as an understanding of their mechanisms emerges.

B cells and transplantation tolerance

This Review comprises a discussion of the mechanisms involved in the induction of B-cell tolerance and a survey of current and emerging therapies that target the effects of B cells in transplant recipients.

Antibodies and ABO‐incompatibility in pediatric transplantation

  • L. West
  • Medicine
    Pediatric transplantation
  • 2011
The unique immunologic nature of infants that the experience reveals has resulted in organ allocation practices evolving in Canada and the UK that facilitate access of children to ABOincompatible donors; thus, patients are listed for transplantation using the first available donor of suitable size, regardless of blood type.

Cryptic B Cell Response to Renal Transplantation

The increase in frequency of donor‐specific antibody‐secreting cells after renal transplantation indicates that B cells respond specifically to the transplant donor more often than previously thought.



ABO-incompatible heart transplantation in infants.

ABO-incompatible heart transplantation can be performed safely during infancy before the onset of isohemagglutinin production and contributes to a marked reduction in mortality among infants on the waiting list.


ABO-incompatible heart transplantation can be performed safely during infancy before the onset of isohemagglutinin production; this technique thus contributes to a marked reduction in mortality among infants on the waiting list.

Immunosuppressive therapy abrogates unresponsiveness to renal allograft induced by thymic recognition of donor antigens.

The effect of the intrathymic injection of donor cells of inducing unresponsiveness to a subsequent kidney graft was abolished by concomitant immunosuppression.

Evidence that the continued presence of the organ graft and not peripheral donor microchimerism is essential for maintenance of tolerance to alloantigen in vivo in anti-CD4 treated recipients.

It is shown that the vascularized cardiac allograft is essential for the maintenance of tolerance to donor alloantigen in vivo, as assessed by the survival of a second heart graft, and tolerance was lost 200 days later.

The cellular mechanism of maintenance of neonatally induced tolerance to H-2 class I antigens.

Investigation of the mechanism by which in vitro cytotoxic T lymphocyte (CTL) hyporeactivity is maintained in adult mice that had been neonatally tolerized to major histocompatibility complex-encoded antigens concludes that this cytotoxicity deficiency is the consequence of in vivo mediated clonal inactivation of the precursors of tolerogen-specific CTL.

Thymic microchimerism correlates with the outcome of tolerance-inducing protocols for solid organ transplantation.

In rats, donor leukocyte infusion is better than donor BM for inducing graft tolerance, defined by long-term graft survival, donor-specific T cell hyporesponsiveness, and reduced interferon gamma production.

Prevention by thymectomy of tolerance induced by intrathymic injection of donor splenocytes.

The presence of the thymus for at least 7 days after intrathymic alloantigen injection and intraperitoneal ALS allows the development of indefinite donor-specific cardiac allograft tolerance.

Role of the Thymus in Transplantation Tolerance in Miniature Swine. I. Requirement of the Thymus for Rapid and Stable Induction of  Tolerance to Class I–mismatched Renal Allografts

It is indicated that the thymus is required for rapid and stable induction of tolerance in miniature swine by performing a complete thymectomy 21 d before renal transplantation.


The results imply an active role for chimeric cells which is best understood as an immune response involving proliferation driven by the idiotypes of the alloreceptors on host cells.