title: Presence of human chromosome 1 with expression of human decay-accelerating factor (DAF) prevents lysis of mouse/human hybrid cells by human complement.
abstract: Xenogeneic organs transplanted to phylogenetically distant species are subject to rapid destruction mediated by complement. In humans, the complement activation is regulated by several proteins encoded by a series of closely linked genes (RCA locus) located on chromosome 1. The mouse/human hybrid cell line B10 was found to have retained human chromosome 1. FACS analysis confirmed that RCA products such as decay-accelerating factor (DAF) were expressed on the membrane surface of B10 cells. When exposed to human or rabbit complement in the presence of 'naturally occurring' human anti-mouse antibodies these cells were not lysed by human complement but were killed by rabbit complement. This effect could be abrogated by addition of anti-DAF monoclonal antibody (IC6). The results offer potential for genetic manipulation of the human complement regulatory products in animals to overcome xenograft hyperacute rejection.
authors.affiliation: Department of Surgery, University of Cambridge Clinical School, Addenbrooke's Hospital, UK.
authors.forename: M W
authors.initials: MW
authors.lastname: Wang
authors.forename: L J
authors.initials: LJ
authors.lastname: Wright
authors.forename: M J
authors.initials: MJ
authors.lastname: Sims
authors.forename: D J
authors.initials: DJ
authors.lastname: White
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D018958:CD55 Antigens; D002460:Cell Line; D002878:Chromosomes, Human, Pair 1; D003169:Complement Inactivator Proteins / Q000502:physiology*; D003165:Complement System Proteins / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D014183:Transplantation, Heterologous
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D018958:CD55 Antigens; D003169:Complement Inactivator Proteins; D008565:Membrane Proteins; D003165:Complement System Proteins