title: Development of B-cell memory in early childhood and the impact on antigen-specific tolerance after heart transplantation.
abstract: BACKGROUND
  Young children show better survival after heart transplant compared with older individuals and can receive heart transplants safely from ABO-incompatible donors. Children develop immunologic tolerance to donor ABH antigens reflected in persistent absence of specific antibodies. We hypothesized that immature T-independent B-cell response and lack of B-cell memory play a crucial role in tolerance of ABH antigens after ABOi transplants.
  
  
  METHODS
  We determined phenotypes of splenic lymphocytes from adults and children and peripheral blood from ABO-incompatible or ABO-compatible heart transplant recipients and control subjects by flow cytometry. In vitro immune response to T-independent stimulation, erythrocytes, and ABH antigens was assessed using proliferation assays.
  
  
  RESULTS
  A predominant role for CD27(+) B cells in T-independent activation was demonstrated; these cells were significantly less frequent in infants than older subjects. Only IgM(+)CD27(+) B cells proliferated in response to non-self erythrocytes. In blood, IgM(+) and switched IgM(-) memory B cells were rare in infants, increasing to near-adult levels in children 5 years old. IgM(+)CD27(+) B cells were significantly fewer in ABO-incompatible transplant recipients than in ABO-compatible recipients.
  
  
  CONCLUSIONS
  CD27(+) cells play a key role in T-independent B-cell activation. Response to ABH antigens is mediated by IgM(+)CD27(+) B cells, and donor ABO-specific tolerance after ABO-incompatible transplantation in children is facilitated by low prevalence of these cells. The pattern of B-cell memory development is altered after ABO-incompatible transplant. Memory B cells may be quantified to assess eligibility for ABO-incompatible transplant and represent a potential therapeutic target to extend the benefits of the immature immune system to older age groups.
authors: Department of Pediatrics; Alberta Transplant Institute; Department of Medical Microbiology and Immunology. Electronic address: urschel@ualberta.ca.
authors: Simon
authors: S
authors: Urschel
authors: Department of Pediatrics; Alberta Transplant Institute.
authors: Lauren A
authors: LA
authors: Ryan
authors: Department of Pediatrics; Alberta Transplant Institute.
authors: Ingrid
authors: I
authors: M Larsen
authors: Department of Pediatrics; Alberta Transplant Institute.
authors: Kimberley
authors: K
authors: Biffis
authors: Department of Pediatrics; Alberta Transplant Institute.
authors: I Esme
authors: IE
authors: Dijke
authors: Department of Pediatrics; Alberta Transplant Institute; Department of Medical Microbiology and Immunology; Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors: Lori J
authors: LJ
authors: West
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology; D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001787:Blood Group Incompatibility / Q000453:epidemiology / Q000276:immunology*; D002170:Canada / Q000453:epidemiology; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D006084:Graft Rejection / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D006085:Graft Survival; D016027:Heart Transplantation; D006801:Humans; D007108:Immune Tolerance; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D015996:Survival Rate / Q000639:trends; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D000017:ABO Blood-Group System
keywords: ABO incompatible transplantation; T-independent B-cell activation; immature immune system; memory B-cells; pediatric heart transplantation; polysaccharide response; tolerance