Evidence that polyreactive antibodies are deposited in rejected discordant xenografts

Robin L. Geller, Fritz H. Bach, Martin A. Turman, Paolo Casali, Jeffrey L. Platt

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The rejection of organs transplanted between phylo-genetically 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 hybrid-oma-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.

Original languageEnglish (US)
Pages (from-to)168-172
Number of pages5
JournalTransplantation
Volume55
Issue number1
DOIs
StatePublished - Jan 1993
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation

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