Presence of human chromosome 1 with expression of human decay-accelerating factor (DAF) prevents lysis of mouse/human hybrid cells by human complement.
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.
Wang
M W
MW
Department of Surgery, University of Cambridge Clinical School, Addenbrooke's Hospital, UK.
Wright
L J
LJ
Sims
M J
MJ
White
D J
DJ
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
D000906:Antibodies; D000911:Antibodies, Monoclonal; D018958:CD55 Antigens; D003169:Complement Inactivator Proteins; D008565:Membrane Proteins; D003165:Complement System Proteins