title: B cell apoptosis accelerates the onset of murine lupus.
abstract: 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.
authors.affiliation: Laboratoire d'Immunologie, Hôpital et Faculté de Médecine Cochin, AP-HP, Université Paris V, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Trébéden-Nègre
authors.forename: Bernard
authors.initials: B
authors.lastname: Weill
authors.forename: Catherine
authors.initials: C
authors.lastname: Fournier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
mesh_terms: 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
chemical_list: 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