Expression of the chemokine receptor CCR2 on immature B cells negatively regulates their cytoskeletal rearrangement and migration

Expression of the chemokine receptor CCR2 on immature B cells negatively regulates their cytoskeletal rearrangement and migration
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DOI:
10.1182/blood-2003-11-4013
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发表时间:
2004-08-15
期刊:
影响因子:
20.3
通讯作者:
Shachar, I
Shachar, I
中科院分区:
医学1区
文献类型:
--
作者:
Flaishon, L;Becker-Herman, S;Shachar, I

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未成熟的B细胞被定位于脾中的特定区域,在那里,这些细胞中的一小部分接收诱导它们成熟并参与免疫反应的信号。在这项研究中,我们发现C-C趋化因子受体2(CCR2)在未成熟的B细胞中转录,而其信息在成熟阶段显著下调。CCR2缺失的细胞表现出趋化因子诱导的肌动蛋白聚合、迁移和归巢到未成熟B细胞的淋巴结的上调。此外,我们证明了CCR2对归巢的控制是由其配体CCL2/JE介导的,CCL2/JE由B细胞分泌,并下调基质衍生因子-1(SDF-1)的信号级联。因此,这项研究描述了CCR2及其配体作为未成熟B细胞归巢的负面调节因子的额外作用,这是以前未确定的。(C)2004年,由美国血液病学会提供。
Immature B cells are targeted to specific areas in the spleen, where a fraction of these cells receive signals that induce them to mature and participate in the immune response. In this study, we show that the C-C chemokine receptor 2 (CCR2) is transcribed in immature B cells, while its message is dramatically down-regulated at the mature stage. CCR2-deficient cells exhibit upregulation of chemokine-induced actin polymerization, migration, and homing to the lymph nodes of immature B cells. In addition, we demonstrate that control of homing by CCR2 is mediated by its ligand, CCL2/JE, which is secreted by B cells and down-regulates the stromal derived factor-1 (SDF-1) signaling cascade. Thus, this study describes an additional, previously uncharacterized, role for CCR2 and its ligand as negative regulators of the homing of immature B cells. (C) 2004 by The American Society of Hematology.