title: The Rho GTPase Cdc42 Is Essential for the Activation and Function of Mature B Cells.
abstract: The Rho GTPase Cdc42 coordinates regulation of the actin and the microtubule cytoskeleton by binding and activating the Wiskott-Aldrich syndrome protein. We sought to define the role of intrinsic expression of Cdc42 by mature B cells in their activation and function. Mice with inducible deletion of Cdc42 in mature B cells formed smaller germinal centers and had a reduced Ab response, mostly of low affinity to T cell-dependent Ag, compared with wild-type (WT) controls. Spreading formation of long protrusions that contain F-actin, microtubules, and Cdc42-interacting protein 4, and assumption of a dendritic cell morphology in response to anti-CD40 plus IL-4 were impaired in Cdc42-deficient B cells compared with WT B cells. Cdc42-deficient B cells had an intact migratory response to chemokine in vitro, but their homing to the B cell follicles in the spleen in vivo was significantly impaired. Cdc42-deficient B cells induced a skewed cytokine response in CD4(+) T cells, compared with WT B cells. Our results demonstrate a critical role for Cdc42 in the motility of mature B cells, their cognate interaction with T cells, and their differentiation into Ab-producing cells.
authors: Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden;
authors: Natalija
authors: N
authors: Gerasimcik
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden;
authors: Carin I M
authors: CI
authors: Dahlberg
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden;
authors: Marisa A P
authors: MA
authors: Baptista
authors: Division of Immunology, Boston Children's Hospital, Boston, MA 02115; and Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
authors: Michel J
authors: MJ
authors: Massaad
authors: Division of Immunology, Boston Children's Hospital, Boston, MA 02115; and Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
authors: Raif S
authors: RS
authors: Geha
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden;
authors: Lisa S
authors: LS
authors: Westerberg
authors: Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden; eva.severinson@su.se.
authors: Eva
authors: E
authors: Severinson
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020764:cdc42 GTP-Binding Protein / Q000276:immunology*
chemical_list: C581598:Cdc42 protein, mouse; D020764:cdc42 GTP-Binding Protein