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

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_3AB2A62512A7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome.
Journal
Blood
Author(s)
Volpi S., Santori E., Abernethy K., Mizui M., Dahlberg C.I., Recher M., Capuder K., Csizmadia E., Ryan D., Mathew D., Tsokos G.C., Snapper S., Westerberg L.S., Thrasher A.J., Candotti F., Notarangelo L.D.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
127
Number
2
Pages
216-220
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
Animals, Autoimmunity/genetics, B-Lymphocytes/immunology, B-Lymphocytes/metabolism, Cell Differentiation/genetics, Cell Differentiation/immunology, Gene Deletion, Mice, Mice, Knockout, Receptors, Antigen, B-Cell/metabolism, Signal Transduction/immunology, Wiskott-Aldrich Syndrome/genetics, Wiskott-Aldrich Syndrome/immunology, Wiskott-Aldrich Syndrome Protein, Neuronal/genetics, Wiskott-Aldrich Syndrome Protein, Neuronal/physiology
Pubmed
Web of science
Open Access
Yes
Create date
09/11/2015 16:16
Last modification date
20/08/2019 13:30
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