Discriminating gene expression profiles of memory B cell subpopulations.

Discriminating gene expression profiles of memory B cell subpopulations.
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DOI:
10.1084/jem.20072682
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发表时间:
2008-08-04
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Cooper MD
Cooper MD
中科院分区:
其他
文献类型:
--
作者:
Ehrhardt GR;Hijikata A;Kitamura H;Ohara O;Wang JY;Cooper MD

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人类记忆B(BMem)细胞的形态学和功能上不同的亚群可通过其CD27或Fc受体样4(FCRL 4)(一种含有具有强抑制潜力的受体的免疫球蛋白结构域)的表达来识别。我们对FCRL 4+和FCRL 4 − BMem细胞进行了比较转录组和蛋白质组分析,发现这两个亚群对编码转录因子、细胞表面蛋白、细胞内信号分子和细胞周期状态调节剂的基因具有非常独特的表达谱。在差异表达的转录因子中,FCRL 4 −细胞中的Runt相关转录因子1(RUNX1)转录水平上调,而FCRL 4+细胞中优先检测到RUNX2转录物。FCRL 4启动子响应性和体内启动子占用的体外证据表明,RUNX转录因子参与这些BMem细胞亚群的产生。FCRL 4 + BMem细胞的独特特征谱是通过其表达CD 11 c、核因子κB配体的受体激活剂和FAS细胞表面蛋白,以及SOX 5、RUNX 2、DLL1和AICDA表达水平升高来定义的。我们的结论是,这个最近确定的BMem细胞亚群,通常居住在上皮组织为基础的壁龛,可能在粘膜防御中发挥独特的作用,相反,作为肿瘤转化事件的目标。
Morphologically and functionally distinct subpopulations of human memory B (BMem) cells are identifiable by either their expression of CD27 or Fc receptor–like 4 (FCRL4), an immunoglobulin domain containing a receptor with strong inhibitory potential. We have conducted comparative transcriptome and proteome analyses of FCRL4+ and FCRL4− BMem cells and found that these two subsets have very distinctive expression profiles for genes encoding transcription factors, cell-surface proteins, intracellular signaling molecules, and modifiers of the cell-cycle status. Among the differentially expressed transcription factors, runt-related transcription factor 1 (RUNX1) transcript levels were up-regulated in FCRL4− cells, whereas RUNX2 transcripts were preferentially detected in FCRL4+ cells. In vitro evidence for FCRL4 promoter responsiveness and in vivo promoter occupancy suggested that RUNX transcription factors are involved in the generation of these BMem cell subpopulations. A distinctive signature profile was defined for the FCRL4+ BMem cells by their expression of CD11c, receptor activator for nuclear factor κB ligand, and FAS cell-surface proteins, in combination with increased levels of SOX5, RUNX2, DLL1, and AICDA expression. We conclude that this recently identified subpopulation of BMem cells, which normally resides in epithelial tissue-based niches, may serve a unique role in mucosal defense and, conversely, as a target for neoplastic transformation events.
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