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 bymodulating B-cell receptor (BCR) clustering and internalization.Wehave 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-celldependent 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.

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

Volpi, Stefano;
2015

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 bymodulating B-cell receptor (BCR) clustering and internalization.Wehave 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-celldependent 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.
File in questo prodotto:
File Dimensione Formato  
2015_N-WASP is required for B-cellÔÇômediated autoimmunity in Wiskott-Aldrich syndrome.pdf

accesso chiuso

Tipologia: Documento in versione editoriale
Dimensione 1.32 MB
Formato Adobe PDF
1.32 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/894993
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 18
social impact