[Cell death and lupus].
Programmed cell death, an essential function in all cells, plays a central role in maintaining immune system homeostasis and controlling autoimmune reactions. Cell death may be an essential element in disseminated lupus erythematosus: defective cell death could lead to the development of autoreactive lymphocyte clones and degradation products of cell death could be implicated in autoimmunity induction and onset of renal lesions. Anomalies in programmed cell death have been demonstrated in murine models of lupus: mutations of the fas and fas-ligand genes, which play a known role in programmed cell death, produce the lpr and gld phenotypes associating lymphoproliferation and lupus. Transgenic mice which express Bcl-2 (the product of Bcl-2 inhibits programmed cell death) on B lymphocytes develop a lupus-type autoimmune disease. The role of these types of anomalies in human disease is not yet elucidated. However, cell death, via the degradation fragments of chromatin, could play a role in inducing antibody production and development of renal lesions. The anti-DNA antibodies, with characteristic antigen-induced immune response (clone expansion, class computation and somatic mutations) could be induced by nucleosomes released during cell death. Several arguments favor this mechanism including cation residues of histone nucleosomes which would bind to anionic residues of sulfate heparan and lead to deposit of autoantibodies in the glomerulus. The dual role of cell death is not really contradictory in autoimmune disease controlled by several independent genes, but would be compatible with several different genetic backgrounds.
Fournié
G
G
INSERM U28, Hôpital Purpan, Toulouse.
D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D001323:Autoantibodies / Q000502:physiology; D002843:Chromatin / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology*; D051379:Mice
D001323:Autoantibodies; D002843:Chromatin
Mort cellulaire et lupus.