Presence of Human Chromosome 1 with Expression of Human Decay‐Accelerating Factor (DAF) Prevents Lysis of Mouse/Human Hybrid Cells by Human Complement

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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.