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Arhgap25 Deficiency Leads to Decreased Numbers of Peripheral Blood B Cells and Defective Germinal Center Reactions.


ABSTRACT: Rho family GTPases are critical for normal B cell development and function, and their activity is regulated by a large and complex network of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). However, the role of GAPs in B cell development is poorly understood. In this study, we show that the novel Rac-GAP ARHGAP25 is important for B cell development in mice in a CXCR4-dependent manner. We show that Arhgap25 deficiency in mice leads to a significant decrease in peripheral blood B cell numbers as well as defects in mature B cell differentiation. Arhgap25-/- B cells respond to Ag stimulation in vitro and in vivo but have impaired germinal center formation and decreased IgG1 class switching. Additionally, Arhgap25-/- B cells show evidence of increased baseline motility and augmented chemotaxis to CXCL12. Taken together, these studies demonstrate an important role for Arhgap25 in peripheral B cell development and Ag response.

SUBMITTER: Lindner SE 

PROVIDER: S-EPMC7301639 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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<i>Arhgap25</i> Deficiency Leads to Decreased Numbers of Peripheral Blood B Cells and Defective Germinal Center Reactions.

Lindner Silke E SE   Egelston Colt A CA   Huard Stephanie M SM   Lee Peter P PP   Wang Leo D LD  

ImmunoHorizons 20200520 5


Rho family GTPases are critical for normal B cell development and function, and their activity is regulated by a large and complex network of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). However, the role of GAPs in B cell development is poorly understood. In this study, we show that the novel Rac-GAP ARHGAP25 is important for B cell development in mice in a CXCR4-dependent manner. We show that <i>Arhgap25</i> deficiency in mice leads to a significant decreas  ...[more]

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