Novel follicular dendritic cell molecule, 8D6, collaborates with CD44 in supporting lymphomagenesis by a Burkitt lymphoma cell line, L3055

Novel follicular dendritic cell molecule, 8D6, collaborates with CD44 in supporting lymphomagenesis by a Burkitt lymphoma cell line, L3055
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DOI:
10.1182/blood.v104.11.1812.1812
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发表时间:
2004-08-01
期刊:
影响因子:
20.3
通讯作者:
Choi, YS
Choi, YS
中科院分区:
医学1区
文献类型:
--
作者:
Li, L;Yoon, SO;Choi, YS

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淋巴滤泡是抗原 (Ag) 激活的 B 细胞分化的特殊微环境;淋巴滤泡中的主要基质细胞成分是滤泡树突状细胞(FDC)。同时,大多数B细胞淋巴瘤起源于生发中心,B细胞淋巴瘤的产生和母细胞转化与肿瘤发生早期的FDC密切相关。为了研究 FDC 在淋巴瘤发生中的功能作用,我们建立了诱导肿瘤模型。人类 B 细胞淋巴瘤细胞系 L3055 仅在接种 FDC 细胞系 HK 后才形成实体瘤。此外,体内肿瘤形成需要两种FDC信号分子(FDC-SM),即一种新型蛋白8D6和4G10/CD44,因为对这两种蛋白具有特异性的单克隆抗体(mAb)在接种L3055和HK细胞时完全抑制了淋巴瘤的发生。然而,这两种 FDC-SM 在肿瘤形成中具有不同的功能作用。 FDC-SM-8D6 增强 L3055 细胞增殖,而 FDC-SM4G10/CD44 抑制其凋亡。鉴定这些关键 FDC-SM 的功能可能有助于发现抑制淋巴瘤细胞存活和生长的治疗药物。
The lymphoid follicle is a specialized microenvironment for the differentiation of antigen (Ag)-activated B cells; the major stromal cell components in lymphoid follicle are the follicular dendritic cells (FDCs). At the same time, most of the B-cell lymphomas originate from the germinal center, and the generation and blast transformation of B-cell lymphoma occurs in close association with FDCs in the early stage of tumorigenesis. To study the functional roles of FDCs in lymphomagenesis, we established an inducible tumor model. The human B-cell lymphoma cell line, L3055, formed solid tumors only when inoculated with an FDC line, HK. In addition, 2 FDC-signaling molecules (FDC-SMs), a novel protein 8D6 and 4G10/CD44, are required for tumor formation in vivo, because monoclonal antibodies (mAbs) specific to these 2 proteins inhibited lymphomagenesis completely when they were inoculated with L3055 and HK cells. However, these 2 FDC-SMs have distinct functional roles in tumor formation. FDC-SM-8D6 enhances L3055 cell proliferation, whereas FDC-SM4G10/CD44 inhibits its apoptosis. Identification of the functional roles of these critical FDC-SMs may lead to the discovery of therapeutic drugs that suppress the survival and growth of lymphoma cells.