Li Li, Yoon Sun-Ok, Fu Dan-Dan, Zhang Xin, Choi Yong Sung
Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
Blood. 2004 Aug 1;104(3):815-21. doi: 10.1182/blood-2004-01-0292. Epub 2004 Apr 15.
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-SM-4G10/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.
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原始转化在肿瘤发生的早期与FDC密切相关。为了研究FDC在淋巴瘤发生中的功能作用，我们建立了一种诱导性肿瘤模型。人B细胞淋巴瘤细胞系L3055只有在接种FDC系HK时才形成实体瘤。此外，两种FDC信号分子（FDC-SM），一种新型蛋白8D6和4G10/CD44，是体内肿瘤形成所必需的，因为针对这两种蛋白的单克隆抗体（mAb）在与L3055和HK细胞一起接种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功能作用。FDC-SM-8D6增强L3055细胞增殖，而FDC-SM-4G10/CD44抑制其凋亡。鉴定这些关键FDC-SM的功能作用可能会导致发现抑制淋巴瘤细胞存活和生长的治疗药物。
