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.

中文翻译：

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p190RhoGEF的过表达增强了T细胞依赖性体液免疫反应中的B细胞活化和生发中心形成。

以前，我们报道了CD40刺激从小鼠脾脏分离的B细胞后p190 Rho鸟嘌呤核苷酸交换因子（p190RhoGEF，ARHGEF28）的诱导表达。我们还报道了p190RhoGEF和下游效应分子RhoA是B细胞分化所必需的，尤其是对于浆细胞（PC）分化的诱导。这项研究使用p190RhoGEF转基因（TG）小鼠在B细胞中过表达野生型完整基因的方法，研究了p190RhoGEF在体内B细胞生物学中的作用。用T细胞依赖性抗原免疫这些小鼠显示，TG小鼠的生发中心B细胞和PC群体显着增加。此外，在用从TG小鼠分离的B细胞与从同窝仔对照小鼠分离的T细胞重建的重组激活1（Rag1）敲除小鼠中显示了相似的结果。涉及生发中心反应和PC分化的同种型转换和转录因子的分析也支持细胞反应的发现。这些结果表明p190RhoGEF可能在依赖T细胞的体液免疫反应中的PC分化阶段发挥作用。