Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation.
The Wiskott-Aldrich syndrome (WAS) is a human X-linked immunodeficiency resulting from mutations in a gene (WASP) encoding a cytoplasmic protein implicated in regulating the actin cytoskeleton. To elucidate WASP function, we disrupted the WASP gene in mice by gene-targeted mutation. WASP-deficient mice showed apparently normal lymphocyte development, normal serum immunoglobulin levels, and the capacity to respond to both T-dependent and T-independent type II antigens. However, these mice did have decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Moreover, purified WASP-deficient T cells showed markedly impaired proliferation and antigen receptor cap formation in response to anti-CD3epsilon stimulation. Yet, purified WASP-deficient B cells showed normal responses to anti-Ig stimulation. We discuss the implications of our findings regarding WASP function in receptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans.
Pubmed ID: 9697838 RIS Download
Animals | Antigens, CD28 | B-Lymphocytes | Cell Division | Colitis | Humans | Immunoglobulin M | Immunologic Capping | Lymph Nodes | Lymphocyte Activation | Mice | Mice, Inbred C57BL | Mice, Knockout | Platelet Count | Proteins | Receptor-CD3 Complex, Antigen, T-Cell | T-Lymphocytes | Wiskott-Aldrich Syndrome | Wiskott-Aldrich Syndrome Protein