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首页> 外文期刊>Cellular immunology >Dock5 controls the peripheral B cell differentiation via regulating BCR signaling and actin reorganization
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Dock5 controls the peripheral B cell differentiation via regulating BCR signaling and actin reorganization

机译：Dock5通过调节BCR信号和肌动蛋白重组来控制外围B细胞分化

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摘要

As an atypical guanine nucleotide exchange factor (GEF), Dock5 has been extensively studied in cellular functions. However, the role of Dock5 on B-cell immunity still remain elusive. In this study, we generated a Dock5 knockout mouse model to study the effect of Dock5 deficiency on B cell development, differentiation and BCR signaling. We found that the absence of Dock5 leads to a moderate effect on B cell development in the bone marrow and reduces follicular (FO) and marginal zone (MZ) B cells. Mechanistically, the key positive upstream B-cell receptor (BCR) signaling molecules, CD19 and Brutons tyrosine kinase (Btk), whose activation determines the fate of FO and MZ B cells, is reduced in Dock5 KO B cells upon antigenic stimulation by using total internal reflection fluorscence microscopy (TIRE) and immunoblot. Interestingly we found that the cellular filamentous actin (F-actin), also decreased in Dock5 KO B cells upon stimulation, which, in turn, offers feedback to BCR signaling. Our study has unveiled that Dock5 regulates the peripheral B cell differentiation via controlling the CD19-Btk signaling axis as well as actin reorganization.
机译：作为非典型鸟嘌呤核苷酸交换因子（GEF），Dock5已在蜂窝功能中进行广泛研究。然而，Dock5对B细胞免疫的作用仍然难以难以捉摸。在这项研究中，我们生成了Dock5淘汰鼠标模型，研究了Dock5缺乏对B细胞开发，分化和BCR信号的影响。我们发现，没有Dock5导致骨髓中B细胞发育的中度效果，减少滤泡（FO）和边缘区（MZ）B细胞。机械地，键正上游B细胞受体（BCR）信号分子，CD19和镇静酪氨酸激酶（BTK），其活化确定FO和MZ B细胞的命运，通过使用总共抗原刺激在抗原刺激后降低了Dock5 KO B细胞。内部反射荧光显微镜（轮胎）和免疫印迹。有趣的是，我们发现，在刺激后，Dock5 KO B细胞中的细胞丝状肌动蛋白（F-actin）也降低，反过来，这反馈了BCR信令的反馈。我们的研究推出了Dock5通过控制CD19-BTK信号轴以及肌动蛋白重组来调节外围B细胞分化。

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  • 来源
    《Cellular immunology》 |2019年第2019期|共7页
  • 作者

    Chen Anwei; Yang Di; Xuan Xingtian; Miller Heather; Luo Xiaoyan; Yu Jie; Yang Gangyi; Wang Hua; Liu Chaohong;

  • 作者单位

    Chongqing Med Univ Chongqing Key Lab Child Infect &

    Immun Childrens Hosp Chongqing 400014;

    Chongqing Med Univ Chongqing Key Lab Child Infect &

    Immun Childrens Hosp Chongqing 400014;

    Chongqing Med Univ Dept Hematol &

    Oncol Childrens Hosp Chongqing Peoples R China;

    NIAID Dept Intracellular Pathogens Hamilton MT USA;

    Chongqing Med Univ Dept Dermatol Childrens Hosp Chongqing Peoples R China;

    Chongqing Med Univ Dept Hematol &

    Oncol Childrens Hosp Chongqing Peoples R China;

    Chongqing Med Univ Affiliated Hosp 2 Dept Endocrinol Chongqing 400010 Peoples R China;

    Chongqing Med Univ Dept Dermatol Childrens Hosp Chongqing Peoples R China;

    Chongqing Med Univ Chongqing Key Lab Child Infect &

    Immun Childrens Hosp Chongqing 400014;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Dock5; B cell; BCR (B cell receptor) signaling; Actin;

    机译：Dock5;B细胞;BCR（B细胞受体）信号传导;actin;

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