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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4139-4147. Prepublished online as a Blood First Edition Paper on September 4, 2008; DOI 10.1182/blood-2008-02-140715. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-02-140715v1 112/10/4139    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 Westerberg, L. S. Articles by Notarangelo, L. D. Search for Related Content PubMed PubMed Citation Articles by Westerberg, L. S. Articles by Notarangelo, L. D. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function Lisa S. Westerberg1,2, Miguel A. de la Fuente3,4, Fredrik Wermeling5, Hans D. Ochs6, Mikael C. I. Karlsson5, Scott B. Snapper1,2,*, and Luigi D. Notarangelo3,4,* 1 Gastrointestinal Unit and the Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Boston; 2 Department of Medicine, Harvard Medical School, Boston, MA; 3 Division of Immunology, Children's Hospital, Boston, MA; 4 Department of Pediatrics, Harvard Medical School, Boston, MA; 5 Unit of Clinical Allergy Research, Department of Medicine, Karolinska Institute, Stockholm, Sweden; and 6 Department of Pediatrics, University of Washington School of Medicine, Seattle Development of hematopoietic cells depends on a dynamic actin cytoskeleton. Here we demonstrate that expression of the cytoskeletal regulator WASP, mutated in the Wiskott-Aldrich syndrome, provides selective advantage for the development of naturally occurring regulatory T cells, natural killer T cells, CD4+ and CD8+ T lymphocytes, marginal zone (MZ) B cells, MZ macrophages, and platelets. To define the relative contribution of MZ B cells and MZ macrophages for MZ development, we generated wild-type and WASP-deficient bone marrow chimeric mice, with full restoration of the MZ. However, even in the presence of MZ macrophages, only 10% of MZ B cells were of WASP-deficient origin. We show that WASP-deficient MZ B cells hyperproliferate in vivo and fail to respond to sphingosine-1-phosphate, a crucial chemoattractant for MZ B-cell positioning. Abnormalities of the MZ compartment in WASP–/– mice lead to aberrant uptake of Staphylococcus aureus and to a reduced immune response to TNP-Ficoll. Moreover, WASP-deficient mice have increased levels of "natural" IgM antibodies. Our findings reveal that WASP regulates both development and function of hematopoietic cells. We demonstrate that WASP deficiency leads to an aberrant MZ that may affect responses to blood-borne pathogens and peripheral B-cell tolerance. 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] L. D. Notarangelo and R. Badolato Leukocyte trafficking in primary immunodeficiencies J. Leukoc. Biol., March 1, 2009; 85(3): 335 - 343. [Abstract] [Full Text] [PDF]

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