IMMUNOBIOLOGY B cell–intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice
نویسندگان
چکیده
Mike Recher,1 Siobhan O. Burns,2,3 Miguel A. de la Fuente,1,4 Stefano Volpi,1 Carin Dahlberg,5 Jolan E. Walter,1 Kristin Moffitt,6 Divij Mathew,1 Nadine Honke,7 Philipp A. Lang,7 Laura Patrizi,1 Hervé Falet,8 Marton Keszei,9 Masayuki Mizui,10 Eva Csizmadia,11 Fabio Candotti,12 Kari Nadeau,13 Gerben Bouma,2 Ottavia M. Delmonte,1 Francesco Frugoni,1 Angela B. Ferraz Fomin,1 David Buchbinder,14 Emma Maria Lundequist,1 Michel J. Massaad,1 George C. Tsokos,10 John Hartwig,8 John Manis,15 Cox Terhorst,9 Raif S. Geha,1 Scott Snapper,16 Karl S. Lang,7,17 Richard Malley,6 Lisa Westerberg,5 Adrian J. Thrasher,2,3 and Luigi D. Notarangelo1
منابع مشابه
B cell-intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice.
Wiskott Aldrich syndrome (WAS) is caused by mutations in the WAS gene that encodes for a protein (WASp) involved in cytoskeleton organization in hematopoietic cells. Several distinctive abnormalities of T, B, and natural killer lymphocytes; dendritic cells; and phagocytes have been found in WASp-deficient patients and mice; however, the in vivo consequence of WASp deficiency within individual b...
متن کاملWASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function.
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. ...
متن کاملWiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis
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-ce...
متن کاملWASp-deficient B cells play a critical, cell-intrinsic role in triggering autoimmunity
Patients with the immunodeficiency Wiskott-Aldrich syndrome (WAS) frequently develop systemic autoimmunity. Here, we demonstrate that mutation of the WAS gene results in B cells that are hyperresponsive to B cell receptor and Toll-like receptor (TLR) signals in vitro, thereby promoting a B cell-intrinsic break in tolerance. Whereas this defect leads to autoantibody production in WAS protein-def...
متن کاملWASP levels in platelets and lymphocytes of wiskott-aldrich syndrome patients correlate with cell dysfunction.
Wiskott-Aldrich syndrome, an inherited blood cell disorder due to mutations of the X-chromosome gene WASP (Wiskott-Aldrich syndrome protein), was characterized originally by thrombocytopenia, immunodeficiency, and eczema. Whereas platelet dysfunction is severe and consistent, immune defects are clinically variable, ranging from negligible to life threatening. To understand this heterogeneity, w...
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