EVIDENCE THAT POLYREACTIVE ANTIBODIES ARE DEPOSITED IN REJECTED DISCORDANT XENOGRAFTS
EVIDENCE THAT POLYREACTIVE ANTIBODIES ARE DEPOSITED IN REJECTED DISCORDANT XENOGRAFTS
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DOI：
10.1097/00007890-199301000-00031
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发表时间：
1993-01-01
期刊：
影响因子：
6.2
通讯作者：
PLATT, JL
中科院分区：
文献类型：
--
作者：
GELLER, RL;BACH, FH;PLATT, JL
在系统发育不同的物种之间移植的器官被认为是由于受体的天然抗体与供体器官血管内皮细胞的结合而引发的排斥反应。我们最近发现，在人血清中与猪内皮细胞和内皮细胞衍生的糖蛋白反应的异种反应的天然抗体中，是多反应抗体。为了测试排斥异种移植物中是否存在多反应性天然抗体，我们开发了一系列针对多反应性人类单抗103的杂交瘤衍生抗体，我们已经证明它能有效地与猪内皮细胞结合。使用这些抗独特型试剂，我们在一组人血清中以及人、恒河猴和狒狒的脾淋巴细胞表面检测到了携带103独特型的抗体。抗独特型试剂的反应模式类似于IgM的分布，免疫球蛋白沉积在猪到恒河猴和猪到狒狒的异种移植组织中。从这些部位洗脱出来的免疫球蛋白分析表明，它们的抗体表现出天然抗体的抗原结合特征。我们的发现与独特型多反应天然抗体广泛交叉反应的假设是一致的。他们还提示，基于体外检测的多反应和异种反应性IgM可能沉积在异种器官移植物中。
The rejection of organs transplanted between phylogenetically disparate species is thought to be initiated by the binding of naturally occurring antibodies of the recipient to the endothelium lining the blood vessels of the donor organ. We recently showed that among the xenoreactive natural antibodies in human serum that react with porcine endothelial cells and endothelial cell-derived glycoproteins are polyreactive antibodies. To test whether polyreactive natural antibodies are present in rejected xenografts we developed a series of hybridoma-derived antibodies specific for the polyreactive human monoclonal antibody 103, which we have shown to bind efficiently to porcine endothelial cells. Using these antiidiotypic reagents we detected antibodies bearing the 103 idiotype in a panel of human sera and on the surface of lymphocytes in the spleen of humans, rhesus monkeys, and baboons. The antiidiotypic reagents reacted in a pattern similar to the distribution of IgM, with immunoglobulin deposits in tissues obtained from pig-to-rhesus monkey and pig-to-baboon xenografts. Analysis of immunoglobulin eluted from these sites showed that they antibodies display the antigen-binding features of natural antibodies. Our findings are consistent with the hypothesis that idiotypes of polyreactive natural antibodies are broadly crossreactive. They also suggest that the polyreactive and xenoreactive IgM, which have been detected based on in vitro assays, may be deposited in a xenogeneic organ graft.