WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation.
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.
Antón
Inés M
IM
Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
de la Fuente
Miguel A
MA
Sims
Tasha N
TN
Freeman
Sheryl
S
Ramesh
Narayanaswamy
N
Hartwig
John H
JH
Dustin
Michael L
ML
Geha
Raif S
RS
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011554:Pseudopodia / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000199:Actins; D017252:CD3 Complex; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D007075:Immunoglobulin M; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015375:Receptors, Interleukin-2; C491671:Waspip protein, mouse; D007073:Immunoglobulin E