Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells.

Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells.
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血管细胞粘附分子-1 和整合素 VLA-4 介导人 B 细胞前体与培养的骨髓贴壁细胞的粘附。

DOI:
10.1172/jci115403
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发表时间:
1991
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Winslow,JM
Winslow,JM
中科院分区:
--
文献类型:
--
作者:
Ryan,DH;Nuccie,BL;Abboud,CN;Winslow,JM

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骨髓微环境中B细胞前体与辅助细胞的粘附可能是正常早期B细胞发育所必需的。人骨髓B细胞前体比成熟B细胞更强烈地粘附在骨髓来源的成纤维细胞上。为了确定这种粘附的机制,用流式细胞术检测了粘附蛋白在人B前体细胞和细胞系上的表达。极晚抗原(VLA)整合素VLA-4和VLA-5是唯一在B细胞前体中表达水平高于成熟B细胞的粘附蛋白。针对VLA-4的α链和β链的抗体,而不是针对VLA-5的抗体,可以显著阻断未成熟B细胞和细胞系与骨髓源性成纤维细胞的结合。虽然纤连蛋白是VLA-4的配体,但抗纤连蛋白抗体和含有VLA-4结合域的可溶性纤连蛋白片段并没有阻断粘附,这表明VLA-4参与了B细胞前体的粘附,而不是作为纤连蛋白受体。血管细胞粘附分子-1 (VCAM-1)是另一种已知的vcam -4的反受体,在骨髓源性成纤维细胞上被发现,抗VCAM-1显著阻断正常B细胞前体对骨髓源性成纤维细胞的粘附,表明vcam -4/VCAM-1相互作用在B细胞前体粘附骨髓微环境中很重要。图片
Adhesion of B cell precursors to accessory cells in the bone marrow microenvironment may be required for normal early B cell development. Human bone marrow B cell precursors adhere more avidly than mature B cells to bone marrow-derived fibroblasts. To determine the mechanism of this adhesion, expression of adhesion proteins on human B precursor cells and cell lines was measured by flow cytometry. The very late antigen (VLA) integrins VLA-4 and VLA-5 were the only adhesion proteins expressed at higher levels in B cell precursors than mature B cells. Antibodies to the alpha and beta chains of VLA-4, but not VLA-5, significantly blocked binding to bone marrow-derived fibroblasts of immature B cells and cell lines. Although fibronectin is a ligand for VLA-4, anti-fibronectin antibody and a soluble fibronectin fragment containing the VLA-4 binding domain did not block adhesion, suggesting that VLA-4 is involved in adhesion of B cell precursors, but not as a fibronectin receptor. Vascular cell adhesion molecule-1 (VCAM-1), the other known counterreceptor for VLA-4, was identified on bone marrow-derived fibroblasts, and anti-VCAM-1 significantly blocked adhesion of normal B cell precursors to bone marrow-derived fibroblasts, indicating that VLA-4/VCAM-1 interactions are important in adhesion of B cell precursors to the bone marrow microenvironment.Images