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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.

SUBMITTER: Gerasimcik N 

PROVIDER: S-EPMC4416737 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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The Rho GTPase Cdc42 Is Essential for the Activation and Function of Mature B Cells.

Gerasimcik Natalija N   Dahlberg Carin I M CI   Baptista Marisa A P MA   Massaad Michel J MJ   Geha Raif S RS   Westerberg Lisa S LS   Severinson Eva E  

Journal of immunology (Baltimore, Md. : 1950) 20150413 10


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  ...[more]

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