Wiskott-Aldrich Syndrome Protein-Deficient Mice Reveal a Role for WASP in T but Not B Cell Activation

Immunity. 1998 Jul;9(1):81-91. doi: 10.1016/s1074-7613(00)80590-7.

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-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.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • CD28 Antigens / immunology
  • Cell Division
  • Colitis / immunology
  • Humans
  • Immunoglobulin M / immunology
  • Immunologic Capping
  • Lymph Nodes
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Count
  • Proteins / genetics
  • Proteins / physiology*
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology*
  • Wiskott-Aldrich Syndrome Protein
  • Wiskott-Aldrich Syndrome*

Substances

  • CD28 Antigens
  • Immunoglobulin M
  • Proteins
  • Receptor-CD3 Complex, Antigen, T-Cell
  • WAS protein, human
  • Was protein, mouse
  • Wiskott-Aldrich Syndrome Protein