title: Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma.
abstract: Autoimmune polyendocrine syndrome type I (APS I) is an inherited recessive disorder with a progressive immunological destruction of many tissues including the adrenal cortex, the parathyroid glands, and the gonads. APS I is caused by mutations in the AIRE gene (autoimmune regulator), expressed in cells of the thymus and spleen, suggesting a role in central and peripheral tolerance. Aire(-/-) mice replicate the autoimmune features of APS I patients with the presence of multiple autoantibodies and lymphocytic infiltrates in various tissues, but young mice appear clinically healthy. We here report the investigation of 15- to 24-month-old Aire(-/-) mice. We did not observe any endocrinological abnormalities, nor did sera from these mice recognize known APS I autoantigens. Interestingly, however, there was a high frequency of marginal zone B-cell lymphoma in Aire(-/-) mice and liver infiltrates of B cells, suggesting chronic antigen exposure and exaggerated activation. Furthermore, increased numbers of monocytes in blood were identified as well as augmented numbers of metallophilic macrophages in the spleen. We propose that Aire, in addition to its function in the thymus, also has a peripheral regulatory role by controlling the development of antigen-presenting cells (APCs) and marginal zone B-cell activation.
authors.affiliation: Department of Medical Science, Section of Clinical Bacteriology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Signe
authors.initials: S
authors.lastname: Hässler
authors.forename: Chris
authors.initials: C
authors.lastname: Ramsey
authors.forename: Mikael C
authors.initials: MC
authors.lastname: Karlsson
authors.forename: Disa
authors.initials: D
authors.lastname: Larsson
authors.forename: Björn
authors.initials: B
authors.lastname: Herrmann
authors.forename: Björn
authors.initials: B
authors.lastname: Rozell
authors.forename: Magnus
authors.initials: M
authors.lastname: Backheden
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein