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 i s caused by a defective or a missing WAS protein (WASP). Signal mediators i nterleukin-4 (IL-4) and CD40 are important for actin-dependent morphology c hanges in B cells. A possible function of WASP and its interacting partners , Cdc42 and Rac1, was investigated for these changes. It was found that act ive Cdc42 and Rac1 induced filopodia and lamellipodia, respectively, in act ivated B cells. Evidence is given that IL-4 has a specific role in the regu lated cycling of Cdc42 because IL-4 partially and transiently depleted acti ve Cdc42 from detergent extract of activated B cells. WASP-deficient B lymp hocytes were impaired in IL-4- and CD40-dependent induction of polarized an d spread cells. Microvilli were expressed on WASP-deficient B cells, but th ey appeared shorter and less dense in cell contacts than in wild-type cells . In conclusion, evidence is provided for the involvement of Cdc42, Rac1, a nd WASP in the cytoskeletal regulation of B lymphocytes. Aberrations in WAS P-deficient B lymphocytes, described here, provide further evidence that WA S is a cytoskeletal disease of hematopoietic cells. (C) 2001 by The America n Society of Hematology.