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

Immunohorizons. 2020 May 20;4(5):274-281. doi: 10.4049/immunohorizons.2000021.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Chemotaxis
  • GTPase-Activating Proteins / deficiency
  • GTPase-Activating Proteins / metabolism*
  • Germinal Center / cytology
  • Germinal Center / metabolism*
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CXCR4 / metabolism

Substances

  • ARHGAP25 protein, mouse
  • CXCR4 protein, mouse
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • Receptors, CXCR4