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N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Volpi Stefano, Santori Elettra, Abernethy Katrina, Mizui Masayuki, Dahlberg Carin I M, Recher Mike, Capuder Kelly, Csizmadia Eva, Ryan Douglas, Mathew Divij, Tsokos George C, Snapper Scott, Westerberg Lisa S, Thrasher Adrian J, Candotti Fabio, Notarangelo Luigi D,
Project Analysis of RAG-dependent immunodeficiency and autoimmunity
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Original article (peer-reviewed)

Journal Blood
Volume (Issue) 127(2)
Page(s) 216 - 20
Title of proceedings Blood
DOI 10.1182/blood-2015-05-643817


Mutations of the Wiskott-Aldrich syndrome gene (WAS) are responsible for Wiskott-Aldrich syndrome (WAS), a disease characterized by thrombocytopenia, eczema, immunodeficiency, and autoimmunity. Mice with conditional deficiency of Was in B lymphocytes (B/WcKO) have revealed a critical role for WAS protein (WASP) expression in B lymphocytes in the maintenance of immune homeostasis. Neural WASP (N-WASP) is a broadly expressed homolog of WASP, and regulates B-cell signaling by modulating B-cell receptor (BCR) clustering and internalization. We have generated a double conditional mouse lacking both WASP and N-WASP selectively in B lymphocytes (B/DcKO). Compared with B/WcKO mice, B/DcKO mice showed defective B-lymphocyte proliferation and impaired antibody responses to T-cell-dependent antigens, associated with decreased autoantibody production and lack of autoimmune kidney disease. These results demonstrate that N-WASP expression in B lymphocytes is required for the development of autoimmunity of WAS and may represent a novel therapeutic target in WAS.