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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4158-4169. Prepublished online as a Blood First Edition Paper on August 7, 2008; DOI 10.1182/blood-2008-02-140814. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-02-140814v1 112/10/4158    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 Meyer-Bahlburg, A. Articles by Rawlings, D. J. Search for Related Content PubMed PubMed Citation Articles by Meyer-Bahlburg, A. Articles by Rawlings, D. J. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis Almut Meyer-Bahlburg1,*, Shirly Becker-Herman1,*, Stephanie Humblet-Baron2, Socheath Khim1, Michele Weber3, Gerben Bouma4, Adrian J. Thrasher4, Facundo D. Batista3, and David J. Rawlings1,5 1 Department of Pediatrics, Seattle Children's Hospital Research Institute, WA; 2 Center for Cellular and Molecular Therapy, GIGA-R, University of Liege, Liege, Belgium; 3 Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, London, United Kingdom; 4 Centre for Immunodeficiency, University College London and Great Ormond Street Hospital for Children National Health Service (NHS) Trust, London, United Kingdom; and 5 Department of Immunology, University of Washington School of Medicine, Seattle To more precisely identify the B-cell phenotype in Wiskott-Aldrich syndrome (WAS), we used 3 distinct murine in vivo models to define the cell intrinsic requirements for WAS protein (WASp) in central versus peripheral B-cell development. Whereas WASp is dispensable for early bone marrow B-cell development, WASp deficiency results in a marked reduction in each of the major mature peripheral B-cell subsets, exerting the greatest impact on marginal zone and B1a B cells. Using in vivo bromodeoxyuridine labeling and in vitro functional assays, we show that these deficits reflect altered peripheral homeostasis, partially resulting from an impairment in integrin function, rather than a developmental defect. Consistent with these observations, we also show that: (1) WASp expression levels increase with cell maturity, peaking in those subsets exhibiting the greatest sensitivity to WASp deficiency; (2) WASp+ murine B cells exhibit a marked selective advantage beginning at the late transitional B-cell stage; and (3) a similar in vivo selective advantage is manifest by mature WASp+ human B cells. Together, our data provide a better understanding of the clinical phenotype of WAS and suggest that gene therapy might be a useful approach to rescue altered B-cell homeostasis in this disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: WASp stings mature lymphocytes Eva Severinson Blood 2008 112: 3921-3922. [Full Text] [PDF] This article has been cited by other articles: M. Bosticardo, F. Marangoni, A. Aiuti, A. Villa, and M. Grazia Roncarolo Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome Blood, June 18, 2009; 113(25): 6288 - 6295. [Abstract] [Full Text] [PDF] A. Astrakhan, H. D. Ochs, and D. J. Rawlings Wiskott-Aldrich Syndrome Protein Is Required for Homeostasis and Function of Invariant NKT Cells J. Immunol., June 15, 2009; 182(12): 7370 - 7380. [Abstract] [Full Text] [PDF]

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