Strategies for tolerance induction among B cells responding transplantation-associated carbohydrate antigens (with the aim of success in clinical ABO-incompatible transplantation and xenotransplantation

B 细胞响应移植相关糖抗原的耐受诱导策略（目的是在临床 ABO 不相容移植和异种移植中取得成功

基本信息

批准号：
13470237
负责人：
ASAHARA Toshimasa
金额：
$ 9.22万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

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.

对血液A或B碳水化合物确定剂的抗体（AB）产生的特定和持续抑制作用才能成功实现ABO不相容的移植。我们展示了一种新的策略，以特异性消除对A碳水化合物的响应。与人类血型O或B个个体相似，小鼠天然对人类血管A-碳水化合物的ABS天然发生。通过用荧光素标记的合成A-碳水化合物（GalNACα1-3FUCα1-2GAL）结合与牛血清相册（BSA）的表面染色，我们已经证明了B细胞识别含有Mial中A-碳水化合物的B细胞属于CD5^+ CD5^+ CD11B^+ CD11B^+ B-1A属性，这些特性是这些属性，这些特性与这些属性相似。可以通过单次注射与BSA和抗BSA ABS结合的合成A碳水化合物来暂时消除此类B细胞。将这种A碳水化合物施用到循环中导致其特异性结合与相应的B细胞受体，因此通过与细胞毒性成分的相互作用而没有影响其他特异性的B细胞克隆，从而用抗A-碳水化合物的特异性耗尽了B细胞。随后用环孢菌素A治疗可以阻止与B-1A的分化，完全抑制了伴有A碳水化合物的B细胞的重新出现。因此，即使在人类A组的红细胞免疫后，该策略也可以防止产生抗A ABS，同时保持总血清IgM和IgG水平。