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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1941-1948. Prepublished online as a Blood First Edition Paper on May 18, 2006; DOI 10.1182/blood-2006-04-019679. This Article Full Text Full Text (PDF) Supplemental Methods, Data, Table, and Figures All Versions of this Article: blood-2006-04-019679v1 108/6/1941    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hässler, S. Articles by Winqvist, O. Search for Related Content PubMed PubMed Citation Articles by Hässler, S. Articles by Winqvist, O. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma Signe Hässler, Chris Ramsey, Mikael C. Karlsson, Disa Larsson, Björn Herrmann, Björn Rozell, Magnus Backheden, Leena Peltonen, Olle Kämpe, and Ola Winqvist From the Departments of Medical Sciences and Section of Clinical Bacteriology, Uppsala University Hospital, Uppsala, Sweden; Unit of Clinical Allergy Research, Department of Medicine, Karolinska Institutet, Karolinska Hospital, Solna, Sweden; Department of Human Genetics, David Geffen School of Medicine, Gonda Center, University of California Los Angeles, Los Angeles, CA; Division of Clinical Research Center and Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska Hospital at Huddinge, Sweden; Department of Learning, Informatics, Management and Ethics (LIME), Karolinska Institutet, Stockholm, Sweden; Department of Human Molecular Genetics, National Public Health Institute, and Medical Genetics, University of Helsinki, Finland. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. S. B. Wolff, M. M. Erichsen, A. Meager, N. F. Magitta, A. G. Myhre, J. Bollerslev, K. J. Fougner, K. Lima, P. M. Knappskog, and E. S. Husebye Autoimmune Polyendocrine Syndrome Type 1 in Norway: Phenotypic Variation, Autoantibodies, and Novel Mutations in the Autoimmune Regulator Gene J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 595 - 603. [Abstract] [Full Text] [PDF]

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