C1Q BINDS DIRECTLY AND SPECIFICALLY TO SURFACE BLOBS OF APOPTOTIC HUMAN KERATINOCYTES - COMPLEMENT DEFICIENCY AND SYSTEMIC TAPES ERYTHEMATOSUS REVISITED

Complete deficiency of C1q is almost invariably associated with the de velopment of systemic lupus erythematosus. it has been suggested that this association may result from a generalized failure to clear Ag-Ab complexes, However, it has not been demonstrated how such a broad impa irment results in this specific and consistent autoimmune phenotype, i n which photosensitive skin disease is the most prominent manifestatio n, We believe there is another role for the classical pathway in maint aining immune tolerance, Surface blebs of apoptotic keratinocytes are concentrated sources of autoantigens, and these packages may define a novel immune context and challenge self-tolerance if not properly clea red and processed, We demonstrate here that when human keratinocytes a re rendered apoptotic, they also develop the capacity to specifically and directly bind to C1q in the absence of Ab, C1q may mediate Ab-inde pendent clearance of apoptotic keratinocytes, and prevent immunization with autoantigens of cutaneous origin.