B cell apoptosis accelerates the onset of murine lupus.
To investigate whether the increased rate of lymphocyte apoptosis in systemic lupus erythematosus is involved in the onset of the disease, apoptotic or necrotic T or B lymphocytes from various cell lines were injected intraperitoneally into pre-autoimmune (NZBxNZW)F1 mice (BW) and non-autoimmune BALB/c mice. The intraperitoneal production of cytokines and chemokines, the specific T cell response in the spleen, and the production of anti-histone and anti-dsDNA Ab were investigated. The onset of the disease was characterized by creatinine levels and evaluation of glomerular IgG deposits. In BW, but not in BALB/c mice, injection of apoptotic and not necrotic cells up-regulated IL-6 and IL-10 in resident macrophages. Administration of apoptotic cells augmented the number of Th2 and B lymphocytes recruited in the peritoneal cavity. Only the treatment with apoptotic B cells promoted a systemic Th2 autoimmune response to H2 histones, associated with earlier occurrence of high levels of anti-dsDNA autoantibodies, higher creatinine levels and more numerous glomerular IgG deposits than in BW controls not injected with apoptotic B cells. In genetically susceptible mice exposure to apoptotic of B, but not T, lymphocytes can elicit a Th2 response to H2 histones that helps B cell production of anti-dsDNA Ab and finally triggers the onset of lupus.
Trébéden-Nègre
Hélène
H
Laboratoire d'Immunologie, Hôpital et Faculté de Médecine Cochin, AP-HP, Université Paris V, France.
Weill
Bernard
B
Fournier
Catherine
C
Batteux
Frédéric
F
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000276:immunology; D017209:Apoptosis; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000473:pathology*; D018925:Chemokines / Q000096:biosynthesis; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006657:Histones / Q000145:classification / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood; D007678:Kidney Glomerulus / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D015458:Leukemia, T-Cell / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology / Q000473:pathology; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010587:Phagocytosis; D010954:Plasmacytoma / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D018925:Chemokines; D018984:Epitopes, T-Lymphocyte; D006657:Histones; D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA; D003404:Creatinine