Cdc42, Rac1, and the Wiskott-Aldrich syndrome protein are involved in the cytoskeletal regulation of B lymphocytes.

• Patients with the immunodeficiency disorder Wiskott-Aldrich syndrome (WAS) have lymphocytes with aberrant microvilli, and their T cells, macrophages, and dendritic cells are impaired in cytoskeletal-dependent processes. WAS is caused by a defective or a missing WAS protein (WASP). Signal mediators interleukin-4 (IL-4) and CD40 are important for actin-dependent morphology changes in B cells. A possible function of WASP and its interacting partners, Cdc42 and Rac1, was investigated for these changes. It was found that active Cdc42 and Rac1 induced filopodia and lamellipodia, respectively, in activated B cells. Evidence is given that IL-4 has a specific role in the regulated cycling of Cdc42 because IL-4 partially and transiently depleted active Cdc42 from detergent extract of activated B cells. WASP-deficient B lymphocytes were impaired in IL-4-- and CD40-dependent induction of polarized and spread cells. Microvilli were expressed on WASP-deficient B cells, but they appeared shorter and less dense in cell contacts than in wild-type cells. In conclusion, evidence is provided for the involvement of Cdc42, Rac1, and WASP in the cytoskeletal regulation of B lymphocytes. Aberrations in WASP-deficient B lymphocytes, described here, provide further evidence that WAS is a cytoskeletal disease of hematopoietic cells.

Keyword

Animals

Antigens; CD40/pharmacology

B-Lymphocytes/cytology/*drug effects/ultrastructure

Cell Adhesion/drug effects

Cell Movement/drug effects

Cell Polarity/drug effects

Cytoskeleton/*drug effects

Interleukin-4/pharmacology

Mice

Mice; Knockout

Microvilli/drug effects

Nerve Tissue Proteins/metabolism

Proteins/*pharmacology/physiology

Research Support; Non-U.S. Gov't

Signal Transduction/drug effects

Wiskott-Aldrich Syndrome/pathology

cdc42 GTP-Binding Protein/drug effects/*pharmacology/physiology

rac1 GTP-Binding Protein/*pharmacology/physiology

rho GTP-Binding Proteins/pharmacology/physiology

Publication and Content Type

ref (subject category)

art (subject category)