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

Details

Serval ID
serval:BIB_2CDBDE4D0117
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
N-WASP is required for B cell-mediated autoimmunity in the Wiskott-Aldrich syndrome
Journal
BLOOD
Author(s)
Volpi S., Santori E., Abernethy K., Mizui M., Dahlberg C.I.M., 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.
Publication state
In Press
Peer-reviewed
Oui
Pages
1-11
Language
english
Abstract
Mutations of the Wiskott-Aldrich syndrome gene (WAS) are responsible for the Wiskott-Aldrich syndrome, 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 homologue of WASP, and regulates signaling in B cells by modulating B cell receptor (BCR) clustering and internalization. To investigate whether N-WASP expression in B cells plays a role in the development of autoimmunity in WAS, we have generated a double conditional mouse lacking both WASP and N-WASP selectively in B lymphocytes (B/DcKO mouse). As compared to B/WcKO mice, B/DcKO mice showed defective B lymphocyte proliferation in response to simultaneous stimulation via BCR and TLR9, and impaired antibody responses to T cell-dependent antigens. Defective B cell activation in B/DcKO mice was associated with decreased autoantibody production and lack of autoimmune kidney disease, as compared to B/WcKO mice. 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 this disease.
Create date
05/10/2015 8:54
Last modification date
21/08/2019 5:13
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