Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase

Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macrophage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer- deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with anti-bodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity.