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滤泡性非霍奇金淋巴瘤中VLA - 4依赖性黏附

VLA-4-dependent adhesion in follicular non-Hodgkin's lymphomas.

作者信息

Ishii G, Harigaya K, Soeta S, Mikata A

机构信息

First Department of Pathology, School of Medicine, Chiba University, Japan.

出版信息

Hematol Pathol. 1995;9(3-4):155-69.

PMID:8655460
Abstract

The cellular contact between B cells and follicular dendritic cells (FDCs) in the germinal center is thought to play a key role in B-cell maturation and proliferation. The adhesion pathway through the very late antigen 4 (VLA-4) on the B cells and the vascular cell adhesion molecule 1 (VCAM-1) on the FDCs support this binding process. The neoplastic follicular centers in follicular non-Hodgkin's lymphomas (FNHLs) have similar structures and cellular components to those of normal germinal centers, but their interaction between B cells and FDCs may be functionally disturbed. In view of this we analyzed the interaction between VLA-4 and VCAM-1 molecules in the germinal center microenvironment, both in neoplastic and normal follicles. The structural characterization of FNHLs and reactive lymph nodes was studied with indirect immunohistochemical stainings using monoclonal antibodies against VLA-4, VCAM-1, and fibronectin, with special reference to the reaction pattern in the normal and neoplastic follicles. In the reactive follicular centers most B cells did not show a positive reaction for VLA-4, except for moderate reaction products in the B cells of the light zone. In FNHLs, on the other hand, most follicular center B cells were positive for VLA-4. The reaction patterns of VCAM-1 and fibronectin in both normal and neoplastic follicular centers were not basically different. To investigate the interaction of VLA-4 with VCAM-1 in both neoplastic and normal follicular centers, we performed a frozen-section binding assay, which found decreased binding between VLA-4 and VCAM-1 in FNHLs. The results of this study indicated that the microenvironment in neoplastic follicular centers is different from that in their normal counterparts, in terms of the characteristic distribution pattern of the VLA-4-positive B cells, and the functional deterioration of the VCAM-1 on FDCs.

摘要

生发中心内B细胞与滤泡树突状细胞(FDC)之间的细胞接触被认为在B细胞成熟和增殖过程中起关键作用。B细胞上的极迟抗原4(VLA-4)与FDC上的血管细胞黏附分子1(VCAM-1)之间的黏附途径支持了这一结合过程。滤泡性非霍奇金淋巴瘤(FNHL)中的肿瘤性滤泡中心与正常生发中心具有相似的结构和细胞成分,但B细胞与FDC之间的相互作用可能在功能上受到干扰。鉴于此,我们分析了肿瘤性和正常滤泡中生发中心微环境中VLA-4和VCAM-1分子之间的相互作用。使用抗VLA-4、VCAM-1和纤连蛋白的单克隆抗体,通过间接免疫组织化学染色研究了FNHL和反应性淋巴结的结构特征,特别关注正常和肿瘤性滤泡中的反应模式。在反应性滤泡中心,大多数B细胞对VLA-4无阳性反应,除了亮区B细胞中有中等反应产物。另一方面,在FNHL中,大多数滤泡中心B细胞对VLA-4呈阳性。正常和肿瘤性滤泡中心中VCAM-1和纤连蛋白的反应模式基本没有差异。为了研究肿瘤性和正常滤泡中心中VLA-4与VCAM-1的相互作用,我们进行了冰冻切片结合试验,结果发现FNHL中VLA-4与VCAM-1之间的结合减少。这项研究的结果表明,肿瘤性滤泡中心的微环境与其正常对应物不同,体现在VLA-4阳性B细胞的特征性分布模式以及FDC上VCAM-1的功能恶化方面。

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