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

Ji Hye Jeong, Yun Jung Ha, So Yeon Choi, Jee Hae Kim, Yungdae Yun, Jong Ran Lee

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)877-887
Number of pages11
JournalImmunology and Cell Biology
Volume97
Issue number10
DOIs
StatePublished - 1 Nov 2019

Bibliographical note

Funding 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.

Publisher Copyright:
© 2019 Australian and New Zealand Society for Immunology Inc.

Keywords

  • B cells
  • CD40 signaling
  • humoral immune responses
  • p190RhoGEF
  • plasma cells

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