WIP Deficiency Reveals a Differential Role for WIP and the Actin Cytoskeleton in T and B Cell Activation

Immunity. 2002 Feb;16(2):193-204. doi: 10.1016/s1074-7613(02)00268-6.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Animals
  • Antigen-Presenting Cells / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • CD3 Complex / immunology
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Cell Division
  • Cells, Cultured
  • Cytoskeletal Proteins
  • Cytoskeleton / metabolism
  • Immunoglobulin E / blood
  • Immunoglobulin M / blood
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Knockout
  • Pseudopodia / immunology
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology
  • Receptors, Interleukin-2 / biosynthesis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Actins
  • CD3 Complex
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Immunoglobulin M
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Waspip protein, mouse
  • Immunoglobulin E