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B cell Tolerance Mechanisms Following ABO-incompatible Infant Heart Transplant: A Potential Role for CD22 Open Access


Other title
B cell tolerance
ABO-incompatible transplantation
ABO-incompatible infant heart transplantation
Heart transplantation
Heart transplantation in infancy
Memory B cells
Human infants
ABO blood group
B cells
Type of item
Degree grantor
University of Alberta
Author or creator
Biffis, Kimberly M
Supervisor and department
Dr. Lori West (Paediatrics, Surgery and Medical Microbiology and Immunology)
Examining committee member and department
Dr. Robert Ingham (Medical Microbiology and Immunology)
Dr. Colin Anderson (Surgery)
Dr. Simon Urschel (Paediatrics)
Medical Sciences-Paediatrics

Date accepted
Graduation date
Master of Science
Degree level
Due to presumed immune immaturity, infants are able to accept heart transplants across the ABO barrier, a procedure that would result in catastrophic consequences if performed in adults. Our group has demonstrated that following ABO-incompatible heart transplantation (ABOi HTx), infants develop specific B cell tolerance to the A/B antigens of their new graft. (1) A precise understanding of ABO-immunobiology in this setting, including elucidating mechanisms of B cell tolerance to donor A/B antigens, is essential to efforts to expand ABOi HTx beyond the immature immune period and thus reduce organ transplant waitlists, as well as to explore human neonatal tolerance to non-ABO antigens. One of many potential mechanisms of B cell tolerance may involve the B cell surface molecule CD22. CD22 has been recognized as an inhibitory molecule of the B cell. (2-4) Interaction of CD22 with its ligand has been reported to play a role in down-regulation of B cell responses and subsequent B cell tolerance in vivo in animal studies. (2) In this thesis we began to investigate the role of CD22 in B cell tolerance in human infants. We examined expression levels of CD22 on human B cell subsets across the lifespan and found increased expression of CD22 on the splenic CD27+IgM+ B cell subset in infants. To further study the role of CD22 in B cell tolerance, we then developed a FACS protocol to isolate the CD27+IgM+ and CD27-IgM+ B cell subsets. Isolated B cells were then analyzed by ELISPOT to assess whether this fraction contained ABO antibody-secreting B cells (ASC), the cells presumably tolerized in the setting of infant ABOi HTx. Results indicated that the majority of the ABO ASC were derived from the CD27+IgM+ B cell subset from infant and adult samples. Lastly, we optimized a Phospho-specific flow cytometry assay using Ramos cells to measure B cell signaling upon engagement of the B cell receptor (BCR) and CD22. Future plans are to use this assay to investigate isolated primary B cells of infants and older individuals and compare signaling profiles upon engagement of BCR and CD22. Understanding inhibitory signaling pathways in B cells from infants and those beyond infancy may allow us to manipulate the immune system and expand the timeframe in which ABOi HTx can be safely performed.
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
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