The immune response to apoptotic cells.
Programmed cell death (PCD) can be divided into two distinct but linked sequential processes, killing of the cells and removal of the dead cells, which may be a neighboring cell or a professional phagocyte. Following internalization of the apoptotic cell, the phagocyte typically triggers neither the development of a pro-inflammatory response nor the production of autoantibodies directed against apoptotic self antigens. Since apoptotic cells are characterized by translocation of autoantigens such as nucleosomes to the surface of the cell, we tested the hypothesis that excess or abnormally processed apoptotic cells can generate autoantibodies. We have found that syngeneic apoptotic load can induce transient hypergammaglobulinemia, anti-DNA, anticardiolipin, and glomerular depositions in normal mice. Furthermore, we also found that one of the important mechanisms of uptake of apoptotic cells involves opsonization by the complement system, suggesting that deficient states could lead to aberrant handling of apoptotic cells. Therefore, conditions in which apoptotic cells become immunogenic may explain antigen selection in inflammatory and autoimmune conditions, such as in systemic lupus erythematosus (SLE).
Mevorach
D
D
Laboratory for Cellular and Molecular Immunology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Israel. mevdm@netvision.net.il
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D000917:Antibody Formation; D017209:Apoptosis / Q000276:immunology* / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000276:immunology; D005720:Gamma Rays; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000276:immunology; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014185:Transplantation, Isogeneic
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007075:Immunoglobulin M