[PDF][PDF] Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation

SB Snapper, FS Rosen, E Mizoguchi, P Cohen… - Immunity, 1998 - cell.com
SB Snapper, FS Rosen, E Mizoguchi, P Cohen, W Khan, CH Liu, TL Hagemann, SP Kwan…
Immunity, 1998cell.com
Abstract 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-indepedent type II antigens. However, these mice did have …
Abstract
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-indepedent 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-CD3ε 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.
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