Antibody-mediated rejection is central to ABO incompatible transplantation as well as to xenotransplantation. The xenoantigen alpha-Gal has a highly analogous carbohydrate structure to the human blood group antigens, and both require memory B cell activation for antibody production. We hypothesize that B cells, reactive to the alpha-Gal xenoantigen and B blood group antigen, require the presence of fully activated T cells in order to survive and proliferate in vitro, contrary to the traditional theory that humoral response to carbohydrate antigens is a T cell-independent process. When we compared the capacity of B cells to proliferate, we observed that activated T cells were necessary for B cell proliferation even in the presence of carbohydrate-derived antigens. A relevant question was also to investigate the role of a specific class of T cells: the CD1d-restricted iNKT cells, in the activation of alpha-Gal and B blood group-reactive B cells. The iNKT cells have the specificity of being reactive to glycolipids and are capable of producing both T helper 1 and T helper 2 cytokine responses. We therefore wanted to determine the role of the iNKT cells as mediators of a T helper 2-type response when B cells were exposed to a glycolipid antigen expressing the alpha-Gal epitope or the human B blood group antigen. We observed that, if the interaction between B cells and iNKT cells is blocked, neither B cell proliferation nor antibody production occurs. These results suggest therefore the importance of the iNKT cell category of T helper cells in the response to alpha-Gal and ABO-blood group glycolipids.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.116121 |
| Date | January 2008 |
| Creators | Kandeva, Teodora N., 1983- |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Surgical Research.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 003164321, proquestno: AAIMR67066, Theses scanned by UMI/ProQuest. |
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