Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation.
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.
Fan
Xiaohu
X
Infection, Immunity, Injury and Repair Program, Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8, Canada.
Ang
Andrew
A
Pollock-Barziv
Stacey M
SM
Dipchand
Anne I
AI
Ruiz
Phillip
P
Wilson
Gregory
G
Platt
Jeffrey L
JL
West
Lori J
LJ
D000017:ABO Blood-Group System / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000276:immunology*; D006388:Hemagglutinins / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007518:Isoantibodies / Q000276:immunology; D051379:Mice; D023001:Transplantation Tolerance / Q000276:immunology*
D000017:ABO Blood-Group System; D006388:Hemagglutinins; D007518:Isoantibodies