WISKOTT-ALDRICH-SYNDROME PROTEIN-DEFICIENT MICE REVEAL A ROLE FOR WASP IN T-CELL BUT NOT B-CELL ACTIVATION

The Wiskott-Aldrich syndrome (WAS) is a human X-linked immunodeficienc y resulting from mutations in a gene (WASP) encoding a cytoplasmic pro tein implicated in regulating the actin cytoskeleton. To elucidate WAS P function, we disrupted the WASP gene in mice by gene-targeted mutati on. WASP-deficient mice showed apparently normal lymphocyte developmen t, normal serum immunoglobulin levels, and the capacity to respond to both T-dependent and T-indepedent type II antigens. However, these mic e did have decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Moreover, purified WASP-deficient T cel ls showed markedly impaired proliferation and antigen receptor cap for mation in response to anti-CD3 epsilon 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-re ceptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans.