Over-expression of p190RhoGEF enhances B-cell activation and germinal center formation in T-cell-dependent humoral immune responses

Immunol Cell Biol. 2019 Nov;97(10):877-887. doi: 10.1111/imcb.12286. Epub 2019 Aug 27.

Abstract

Previously, we reported induced expression of the p190 Rho guanine nucleotide exchange factor (p190RhoGEF, ARHGEF28) following CD40 stimulation of B cells isolated from mouse spleen. We also reported that p190RhoGEF and a downstream effector molecule RhoA are required for B-cell differentiation, especially for the induction of the plasma cell (PC) differentiation. This study investigates the role of p190RhoGEF in B-cell biology in vivo, using p190RhoGEF transgenic (TG) mice that overexpress a wild-type full gene in B cells. Immunization of these mice with T-cell-dependent antigen showed that populations of germinal center B cells and PCs were significantly increased in TG mice. Furthermore, similar results were shown in recombination activating 1 (Rag1) knockout mice that were reconstituted with B cells isolated from TG mice in combination with T cells isolated from littermate control mice. Analyses of isotype class switching and transcription factors involved in a germinal center reaction and PC differentiation also supported the findings from the cellular responses. These results suggest that p190RhoGEF may play a role in the stage of PC differentiation during T-cell-dependent humoral immune responses.

Keywords: B cells; CD40 signaling; humoral immune responses; p190RhoGEF; plasma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Germinal Center / immunology*
  • Homeodomain Proteins / metabolism
  • Immunity, Humoral*
  • Immunoglobulin Class Switching
  • Lymphocyte Activation / immunology*
  • Mice, Transgenic
  • Plasma Cells / cytology
  • Plasma Cells / metabolism
  • Spleen / metabolism
  • T-Lymphocytes / immunology*
  • ras-GRF1 / metabolism*

Substances

  • Homeodomain Proteins
  • Rasgrf1 protein, mouse
  • ras-GRF1
  • RAG-1 protein