Reference : Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral...
Scientific journals : Article
Human health sciences : Hematology
Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis
Meyer-Bahlburg, A. [ > > ]
Becker-Herman, S. [ > > ]
Humblet, Stéphanie mailto [Université de Liège - ULiège > > GIGA-R : Hématologie >]
Khim, S. [ > > ]
Weber, M. [ > > ]
Bouma, G. [ > > ]
Thrasher, A. J. [ > > ]
Batista, F. D. [ > > ]
Rawlings, D. J. [ > > ]
American Society of Hematology
Yes (verified by ORBi)
[en] 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 funtcional assays, we show that these dificits 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 maturaity, 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.

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