The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4

The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4
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DOI:
10.1002/eji.1830270729
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发表时间:
1997-07-01
影响因子:
5.4
通讯作者:
Moser, B
Moser, B
中科院分区:
医学3区
文献类型:
--
作者:
DApuzzo, M;Rolink, A;Moser, B

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在骨髓中,祖细胞(pro-)和前体B细胞(pre-)依赖于与基质细胞的密切接触来生长和成熟基质细胞衍生因子1 (SDF-1),也称为B细胞前生长刺激因子,由骨髓基质细胞产生,据报道与白细胞介素-7一起作为前B细胞的共丝裂原。SDF-1最近被证明是一种趋化因子,它通过趋化因子受体CXCR4对不同类型的白细胞具有趋化作用。利用B220(+)骨髓细胞和B淋巴形成不同阶段的几种B细胞系,我们现在发现SDF-1对前B细胞和前B细胞是一种有效的引诱剂,但在发育后期对B细胞不起作用。在早期B细胞前体中,SDF-1诱导细胞内Ca2+动员和体外迁移,其效力和功效与趋化因子作用于血液白细胞的效力和功效相似。这些反应是通过CXCR4介导的,因为它们可以被抗受体抗体抑制。SDF-1是第一个显示作用于早期B细胞前体的趋化因子。缺乏SDF-1的小鼠会在围产期死亡,并表现出B淋巴系统的严重缺乏。我们认为,基质细胞释放的SDF-1通过选择性地吸引和限制骨髓微环境中的早期B细胞前体来发挥其关键的造血功能,从而为生长和分化提供必要的因素。
In the bone marrow progenitor (pro-) and precursor (pre-) B cells depend on close contact with stromal cells for growth and maturation Stromal cell-derived factor 1 (SDF-1), also known as pre-B cell growth-stimulating factor, is produced by bone marrow stromal cells and was reported to act together with interleukin-7 as co-mitogen for pre-B cells. SDF-1 was recently shown to be a chemokine which is chemotactic for different typos of leukocytes and acts via the chemokine receptor CXCR4. Using sorted B220(+) bone marrow cells and several B cell lines characteristic for different stages of B lymphopoiesis, we now show that SDF-1 is a potent attractant for pro- and pre-B cells, but is inactive on B cells at later stages of development. In early B cell precursors, SDF-1 induced intracellular Ca2+ mobilization and in vitro migration with a potency and efficacy similar to that observed for chemokines acting on blood leukocytes. These responses were mediated via CXCR4 as they could be inhibited by an anti-receptor antibody SDF-1 is the first chemokine shown to act on early-stage B cell precursors. Mice lacking SDF-1 die perinatally and show a severe deficiency in B lymphopoiesis. We propose that SDF-1 released from the stromal cells exerts its critical hematopoietic function by selectively attracting and confining early B cell precursors within the bone marrow microenvironment that provides the necessary factors for growth and differentiation.