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Title: Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis
Authors: Meyer-Bahlburg, Almut ×
Becker-Herman, Shirly
Humblet-Baron, Stephanie
Khim, Socheath
Weber, Michele
Bouma, Gerben
Thrasher, Adrian J
Batista, Facundo D
Rawlings, David J #
Issue Date: Nov-2008
Publisher: W.B. Saunders
Series Title: Blood vol:112 issue:10 pages:4158-4169
Abstract: 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. (Blood. 2008; 112: 4158-4169)
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Genetics of Autoimmunity
× corresponding author
# (joint) last author

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