title: C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited.
abstract: Complete deficiency of C1q is almost invariably associated with the development 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 impairment results in this specific and consistent autoimmune phenotype, in which photosensitive skin disease is the most prominent manifestation. We believe there is another role for the classical pathway in maintaining 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 cleared and processed. We demonstrate here that when human keratinocytes are rendered apoptotic, they also develop the capacity to specifically and directly bind to C1q in the absence of Ab. C1q may mediate Ab-independent clearance of apoptotic keratinocytes, and prevent immunization with autoantigens of cutaneous origin.
authors.affiliation: Graduate Program in Immunology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Korb
authors.forename: J M
authors.initials: JM
authors.lastname: Ahearn
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D015922:Complement C1q / Q000172:deficiency / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015603:Keratinocytes / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology*; D014466:Ultraviolet Rays
chemical_list: D015922:Complement C1q