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. (Blood. 2001;98:1086-1094)
Westerberg
L
L
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. lisa.westerberg@cmb.ki.se
Greicius
G
G
Snapper
S B
SB
Aspenström
P
P
Severinson
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D019013:CD40 Antigens / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects*; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014923:Wiskott-Aldrich Syndrome / Q000473:pathology; D051316:Wiskott-Aldrich Syndrome Protein; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D020764:cdc42 GTP-Binding Protein / Q000187:drug effects / Q000494:pharmacology* / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000494:pharmacology* / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000494:pharmacology / Q000502:physiology
D019013:CD40 Antigens; D009419:Nerve Tissue Proteins; D011506:Proteins; C495768:Was protein, mouse; C495772:Wasl protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D015847:Interleukin-4; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins