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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.
 Previous Article | Next Article 
Submitted December 22, 2005
Accepted April 28, 2006
Aire deficient mice develop hematopoetic irregularities
and marginal zone B cell lymphoma
Signe Hassler, Chris Ramsey, Mikael C Karlsson, Disa Larsson, Bjorn Herrmann, Bjorn Rozell, Magnus Backheden, Leena Peltonen, Olle Kampe, and Ola Winqvist*
Dept. of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden
Department of Human Genetics, David Geffen School of Medicine, Gonda Center, UCLA, CA, USA
Karolinska Institutet,Dept. of Medicine,Unit of Clinical Allergy Research,Karolinska Hospital,Sweden
Dept. of Medical Sciences, Section of Clinical Bacteriology, Uppsala University Hospital, Uppsala
Karolinska Institutet,Division of Clinical Research Center & Pathology,Karolinska Hospital,Huddinge
Dept. of Learning, Informatics, Management and Ethics (LIME), Karolinska Institutet,Stockholm,Sweden
* Corresponding author; email: ola.winqvist{at}karolinska.se.
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 15-24 months 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 APCs and marginal zone B cell activation.
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