Activation induced differential regulation of stem cell antigen-1 (Ly-6A/E) expression in murine B cells
Activation induced differential regulation of stem cell antigen-1 (Ly-6A/E) expression in murine B cells
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DOI：
10.1016/j.cellimm.2003.09.006
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发表时间：
2003-09-01
影响因子：
4.3
通讯作者：
Muthusamy, N
中科院分区：
文献类型：
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作者：
Chen, HC;Frissora, F;Muthusamy, N
干细胞抗原-1 （Ly-6A/E）的表达在小鼠B细胞中受发育调控。然而，对其在B细胞活化过程中的调节作用知之甚少。我们在此报告了成熟B细胞中不同激活信号对Ly-6A/E表达的差异调节。通过抗原受体（BCR）刺激静止B细胞抑制Ly-6A/E表面表达呈剂量依赖性。激活诱导的Ly-6A/E下调是BCR介导的信号事件特异性的，如抗cd40、脂多糖或干扰素γ刺激B细胞诱导的Ly-6A/E表面表达上调。激活诱导的Ly-6A/E表达的差异调节是在rnRNA水平上介导的。利用STAT-1(-/-) B细胞进一步证实了BCR信号在抑制Ly-6A/E表达中的作用，STAT-1(-/-) B细胞表达构成型而非诱导型Ly-6A/E。BCR诱导的Ly-6A/E RNA和表面表达的抑制作用可被离子霉素模拟，但肉豆蔻酸佛波酯却不能，这表明它与钙有关，而与蛋白激酶C依赖的信号事件无关。抑制钙调磷酸酶逆转BCR或离子霉素抑制Ly-6A/E的表达。有趣的是，对Ly-6A/E+和Ly-6A/E-脾B细胞的体外分化分析显示，Ly-6A/E+细胞是产生抗体的主要来源，这表明Ly-6A/E在B细胞分化中可能发挥作用。这些研究为激活诱导的Ly-6A/E+ B细胞的差异调节和分化提供了第一个证据。(C) 2003 Elsevier Inc.版权所有。
Expression of stem cell antigen-1 (Ly-6A/E) is developmentally regulated in murine B cells. However, little is known about its modulation during B cell activation. We report here the differential regulation of Ly-6A/E expression in response to diverse activation signals in mature B cells. Stimulation of resting B cells through the antigen receptor (BCR) inhibited, Ly-6A/E surface expression in dose dependent manner. Activation induced downregulation of Ly-6A/E is specific to BCR mediated signaling events as stimulation of B cells with anti-CD40, lipopolysaccharide or interferon-gamma induced upregulation of Ly-6A/E surface expression. The activation induced differential modulation of Ly-6A/E expression is mediated at the rnRNA levels. A role for BCR signaling in inhibition of Ly-6A/E expression was further confirmed using STAT-1(-/-) B cells, which expressed constitutive, but not inducible Ly-6A/E. The BCR induced inhibition of Ly-6A/E RNA and surface expression was mimicked by ionomycin, but not phorbol myristate acetate, indicating a role for calcium but not protein kinase C dependent signaling events. Inhibition of calcineurin reversed the BCR or ionomycin inhibited Ly-6A/E expression. Interestingly, in vitro differentiation analysis of Ly-6A/E+ and Ly-6A/E- splenic B cells revealed the Ly-6A/E+ cells to be the major source of antibody production, suggesting a potential role for Ly-6A/E in B cell differentiation. These studies provide the first evidence for activation induced differential modulation and differentiation of Ly-6A/E+ B cells. (C) 2003 Elsevier Inc. All rights reserved.