Ryan D H, Nuccie B L, Abboud C N, Winslow J M
Department of Pathology, University of Rochester Medical Center, New York 14642.
J Clin Invest. 1991 Sep;88(3):995-1004. doi: 10.1172/JCI115403.
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.
骨髓微环境中B细胞前体与辅助细胞的黏附可能是正常早期B细胞发育所必需的。人骨髓B细胞前体比成熟B细胞更强烈地黏附于骨髓来源的成纤维细胞。为了确定这种黏附的机制，通过流式细胞术检测了人B前体细胞和细胞系上黏附蛋白的表达。极晚期抗原（VLA）整合素VLA-4和VLA-5是在B细胞前体中比成熟B细胞表达水平更高的仅有的黏附蛋白。针对VLA-4的α和β链的抗体，而不是VLA-5的抗体，显著阻断了未成熟B细胞和细胞系与骨髓来源的成纤维细胞的结合。尽管纤连蛋白是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未阻断黏附，这表明VLA-4参与B细胞前体的黏附，但不是作为纤连蛋白受体。血管细胞黏附分子-1（VCAM-1），VLA-4的另一个已知的反受体，在骨髓来源的成纤维细胞上被鉴定出来，并且抗VCAM-1显著阻断了正常B细胞前体与骨髓来源的成纤维细胞的黏附，表明VLA-4/VCAM-1相互作用在B细胞前体与骨髓微环境的黏附中起重要作用。
