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 (1C6). The results offer potential for genetic manipulation of the human complement regulatory products in animals to overcome xenograft hyperacute rejection.