title: Lack of the transcriptional coactivator OBF-1 prevents the development of systemic lupus erythematosus-like phenotypes in Aiolos mutant mice.
abstract: Here we show that mice lacking the zinc finger transcription factor Aiolos develop the symptoms of human systemic lupus erythematosus (SLE), which is characterized by the production of anti-dsDNA Ab and immune complex-mediated glomerulonephritis. This finding indicates that normal Aiolos function is necessary to maintain immune homeostasis and suppress the development of systemic autoimmune disease and implicates Aiolos as a possible candidate gene for SLE. Interestingly, Aiolos-null mice can no longer mount autoimmune reactions and completely fail to develop SLE when they are deficient for the B cell-specific transcription coactivator OBF-1. The lack of OBF-1 reverses several Aiolos mutant mouse phenotypes, such as B cell hyperproliferation, high expression of activation marker on B cells, and spontaneous germinal center formation. Unexpectedly, B cell development at the immature B cell stage is severely impaired in the bone marrow of Aiolos/OBF-1 double-deficient mice, demonstrating the key role of these factors in the transition from pre-B to immature B cells. Our results indicate that B cells play a crucial role in the development of SLE in Aiolos mutant mice and might be useful for the strategy of SLE treatment.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Gabriele
authors.initials: G
authors.lastname: Matthias
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: Katia
authors.initials: K
authors.lastname: Georgopoulos
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D006801:Humans; D051740:Ikaros Transcription Factor; D007105:Immune Complex Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007136:Immunoglobulins / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D013234:Stem Cells / Q000276:immunology / Q000473:pathology; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors
chemical_list: D000974:Antibodies, Antinuclear; C106285:IKZF3 protein, human; C491396:Ikzf3 protein, mouse; D007136:Immunoglobulins; C091546:POU2AF1 protein, human; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051740:Ikaros Transcription Factor