Abstract
WIP stabilizes actin filaments and is important for filopodium formation. To define the role of WIP in immunity, we generated WIP-deficient mice. WIP(minus sign/minus sign) mice have normal lymphocyte development, but their T cells fail to proliferate, secrete IL-2, increase their F-actin content, polarize and extend protrusions following T cell receptor ligation, and are deficient in conjugate formation with superantigen-presenting B cells and anti-CD3 bilayers. In contrast, WIP-deficient B lymphocytes have enhanced proliferation and CD69 expression following B cell receptor ligation and mount normal antibody responses to T-independent antigens. Both WIP-deficient T and B cells show a profound defect in their subcortical actin filament networks. These results suggest that WIP is important for immunologic synapse formation and T cell activation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism*
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Animals
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Antigen-Presenting Cells / immunology
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology*
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CD3 Complex / immunology
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Carrier Proteins / genetics
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Carrier Proteins / immunology*
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Cell Division
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Cells, Cultured
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Cytoskeletal Proteins
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Cytoskeleton / metabolism
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Immunoglobulin E / blood
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Immunoglobulin M / blood
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Lymphocyte Activation / immunology*
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Mice
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Mice, Knockout
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Pseudopodia / immunology
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Receptor-CD3 Complex, Antigen, T-Cell / immunology
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Receptors, Interleukin-2 / biosynthesis
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
Substances
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Actins
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CD3 Complex
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Carrier Proteins
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Cytoskeletal Proteins
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Immunoglobulin M
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Receptor-CD3 Complex, Antigen, T-Cell
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Receptors, Interleukin-2
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Waspip protein, mouse
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Immunoglobulin E