Over‐expression of p190RhoGEF enhances B‐cell activation and germinal center formation in T‐cell‐dependent humoral immune responses. Issue 10 (27th August 2019)

• Record Type: Journal Article
• Authors: Jeong, Ji Hye; Ha, Yun Jung; Choi, So‐Yeon; Kim, Jee‐Hae; Yun, Yungdae; Lee, Jong Ran
• Is Part Of: Immunology and cell biology. Volume 97:Issue 10(2019)
• Page Start: 877
• Page End: 887
• Publication Date: 2019-08-27
• Subjects: B cells -- CD40 signaling -- humoral immune responses -- p190RhoGEF -- plasma cells; Immunology -- Periodicals; Cytology -- Periodicals; 616.079
• DOI: 10.1111/imcb.12286
• Languages: English
• ISSNs: 0818-9641

Abstract

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. Abstract : Expression of the p190 Rho guanine nucleotide exchange factor (p190RhoGEF) was induced following CD40 stimulation in B cells. To investigate whether p190RhoGEF may play a role during T‐cell‐dependent humoral immune responses, antigen‐driven B‐cell differentiation was analyzed in transgenic mice, in which B cells constitutively express a wild‐type full gene of p190RhoGEF. Germinal center formation, plasma cell differentiation and isotype class switching are enhanced in these transgenic mice in response to immunization with a T‐cell‐dependent antigen.