N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome.
Blood
; 127(2): 216-20, 2016 Jan 14.
Article
in En
| MEDLINE
| ID: mdl-26468226
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Wiskott-Aldrich Syndrome
/
B-Lymphocytes
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Autoimmunity
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Wiskott-Aldrich Syndrome Protein, Neuronal
Limits:
Animals
Language:
En
Journal:
Blood
Year:
2016
Type:
Article