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.
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Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 02115, USA.
Rosen
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FS
Mizoguchi
E
E
Cohen
P
P
Khan
W
W
Liu
C H
CH
Hagemann
T L
TL
Kwan
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Ferrini
R
R
Davidson
L
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Bhan
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AK
Alt
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D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D002455:Cell Division; D003092:Colitis / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007152:Immunologic Capping; D008198:Lymph Nodes; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010976:Platelet Count; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014923:Wiskott-Aldrich Syndrome; D051316:Wiskott-Aldrich Syndrome Protein
D018106:CD28 Antigens; D007075:Immunoglobulin M; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C495767:WAS protein, human; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein