Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks
N-WASP is required for B-cell–mediated autoimmunity in Wiskott-Aldrich syndrome
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4407646
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.
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.