title: B cells are critical for autoimmune pathology in Scurfy mice.
abstract: Impaired regulatory T-cell function results in a severe chronic autoimmune disease affecting multiple organs in Scurfy mice and humans with the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Previous studies have shown that T helper cells but not cytotoxic T cells are critical for the disease pathology. Whether this T-cell subset is responsible directly for tissue inflammation or rather indirectly via the interaction with B cells or myeloid cells is largely unknown. To study this and to identify potential therapeutic targets for this lethal disease we investigated the contribution of B cells to this complex autoimmune phenotype. We show that B cells and the production of autoantibodies plays a major role for skin, liver, lung, and kidney inflammation and therapeutic depletion of B cells resulted in reduced tissue pathology and in prolonged survival. In contrast, the absence of B cells did not impact systemic T-cell activation and hyperreactivity, indicating that autoantibody production by B cells may be a major factor for the autoimmune pathology in mice deficient for regulatory T cells.
authors.affiliation: Institute of Genetics, Department of Biology, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Aschermann
authors.forename: Christian H K
authors.initials: CH
authors.lastname: Lehmann
authors.forename: Sidonia
authors.initials: S
authors.lastname: Mihai
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Diana
authors.initials: D
authors.lastname: Dudziak
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000378:metabolism*; D001806:Blood Urea Nitrogen; D003922:Diabetes Mellitus, Type 1 / Q000151:congenital; D003967:Diarrhea; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000276:immunology; D007154:Immune System Diseases / Q000151:congenital; D007108:Immune Tolerance / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse