Effect of the B cell superantigen protein A from S. aureus on the early lupus disease of (NZBxNZW) F1 mice.
The (NZBxNZW) F(1) mouse develops a spontaneous autoimmune disease process with striking similarities to human systemic lupus erythematosus (SLE). In female (NZBxNZW) F(1) mice, the production of IgG antinuclear antibodies, including antibodies to double-stranded DNA (dsDNA), is associated with the development of a severe immune complex-mediated glomerulonephritis that results in death from renal failure in virtually all animals by 12 months of age. Since B-1 and marginal zone (MZ) cells represent a potential source of pathogenic antibodies and because B cell superantigens have been demonstrated to reduce B-1 and MZ cells in vivo, we tested the effect of repeated injections of the superantigen protein A (SpA) from S. aureus on the disease of this lupus model. We found that weekly intraperitoneal injections of SpA delay the progression of serum anti-DNA IgG and reduce proteinuria early in young female (NZBxNZW) F(1) mice. This superantigen also induced a specific depression in the numbers of peritoneal B-1 cells, as compared to mice treated with a control protein. These results support the role of B-1 cells in the development of the autoimmune disease in this mouse model and suggest that B cell superantigens may be useful in the management of autoimmune conditions.
Viau
Muriel
M
Institut National de Santé et de Recherche Médicale (INSERM U 430), Unite d'Immunopathologie Humaine, 15 rue de l'Ecole de Médecine, F-75006 Paris, France.
Zouali
Moncef
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D016175:B-Lymphocyte Subsets; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010529:Peritoneal Cavity / Q000166:cytology; D011507:Proteinuria; D013154:Spleen / Q000166:cytology; D013205:Staphylococcal Protein A / Q000627:therapeutic use*; D013211:Staphylococcus aureus; D018089:Superantigens / Q000627:therapeutic use
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; D018089:Superantigens