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.
Bibliographical noteFunding Information:
We thank Drs W Moolenaar and D Mathis for providing p190RhoGEF plasmid and pDOI expression vector, respectively. This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean Government (2009-0067361, 2011-0016543, 2015R1A2A2A01004209 and 2019R1A2C1007743 to JRL, and 2012R1A5A1048236 to YY and JRL). JHJ and YJH were supported in part by the Brain Korea 21 Program of the Korea Ministry of Education.
© 2019 Australian and New Zealand Society for Immunology Inc.
- B cells
- CD40 signaling
- humoral immune responses
- plasma cells