Exp Mol Med.  2012 Feb;44(2):138-148. 10.3858/emm.2012.44.2.009.

Increased p190RhoGEF expression in activated B cells correlates with the induction of the plasma cell differentiation

• Ha YJ
• Jeong JH
• Park Y
• Lee JR

• KMID: 1120132
• DOI: http://doi.org/10.3858/emm.2012.44.2.009

Abstract

Previously, we demonstrated that the p190 Rho guanine nucleotide exchange factor (p190RhoGEF) was induced following CD40 stimulation of B cells. In this study, we examined whether p190RhoGEF and a downstream effector molecule RhoA are required for B cell differentiation. Expression of p190RhoGEF positively correlated with the expression of surface markers and transcriptional regulators that are characteristic of mature B cells with plasma cell (PC) phenotypes. Moreover, either the overexpression of p190RhoGEF or the expression of a constitutively active RhoA drove cellular differentiation toward PC phenotypes. B cell maturation was abrogated in cells that overexpressed p190RhoGEF and a dominant-negative form of RhoA simultaneously. CD40-mediated maturation events were also abrogated in cells that overexpressed either dominant-negative p190RhoGEF or RhoA. Together, these data provide evidence that p190RhoGEF signaling through RhoA in CD40-activated B cells drives the induction of the PC differentiation.

Keyword

antigens, CD40; ARHGAP35 protein, human; B-lymphocytes; CD40; cell differentiation; p190RhoGEF; plasma cells; rhoA GTP-binding protein

MeSH Terms

Animals
B-Lymphocytes/*cytology/*metabolism
Cell Differentiation/genetics/*physiology
Cell Line
Cells, Cultured
Female
Guanine Nucleotide Exchange Factors/genetics/*metabolism
Humans
Lymphocyte Activation/genetics/*physiology
Mice
Mice, Inbred BALB C
Plasma Cells/*cytology/*metabolism
rhoA GTP-Binding Protein/genetics/metabolism