2003 Fiscal Year Final Research Report Summary
Strategies for tolerance induction among B cells responding transplantation-associated carbohydrate antigens (with the aim of success in clinical ABO-incompatible transplantation and xenotransplantation
| Project/Area Number |
13470237
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Hiroshima University |
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Principal Investigator |
ASAHARA Toshimasa Hiroshima University, Graduate School of Biomedical Science, Professor, 大学院・医歯薬学総合研究科, 教授 (70175850)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIOKA Shinkichiro Hiroshima University, Medical and Dental Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (30284194)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Organ Transplantation / ABO-incompatible transplantation / Xenotransplantation / Tolerance / B cells / Immuno-toxin |
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| Research Abstract |
The specific and persistent inhibition of antibody (Ab) production against blood group A or B carbohydrate determinants would be required to succeed ABO-incompatible transplantation. We here demonstrated a novel strategy for specific elimination of B cells responding to A-carbohydrates. Resembling to human blood group O or B individuals, mice had naturally occurring Abs against human blood group A-carbohydrates in their sera. By surface staining with fluoresceine-labeled synthetic A-carbohydrates (GalNAcα1-3 Fucα1-2Gal) conjugated to bovine serum albumin (BSA), we have demonstrated that B cells bearing receptors recognizing A-carbohydrates in mice belong to CD5^+ CD11b^+ B-1a subset, similarly to the phenotypic property of those in humans. Such B cells could be temporarily eliminated by single injection of synthetic A-carbohydrates conjugated with BSA and anti-BSA Abs. Administration of such A-carbohydrates into the circulation resulted in its specific binding to the corresponding B cell receptors, and consequently depleted the B cells with the anti-A-carbohydrates specificity via the interaction with the cytotoxic constituent without affecting B cell clones with other specificity. Subsequent treatment with cyclosporin A, which could block differentiation to B-1a, completely inhibited reappearance of B cells bearing receptor for A-carbohydrates. This strategy thereby prevented production of anti-A Abs even after immunization with human group A erythrocytes, while maintaining total serum IgM and IgG levels.
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