Follicular dendritic cells protect malignant B cells from apoptosis induced by anti-Fas and antineoplastic agents.
Follicular dendritic cells protect malignant B cells from apoptosis induced by anti-Fas and antineoplastic agents.
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DOI：
10.4049/jimmunol.163.12.6442
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发表时间：
1999-12
影响因子：
4.4
通讯作者：
Y. X. Schwarz;M. Yang;D. Qin;J. Wu;W. Jarvis;S. Grant;G. F. Burton;A. Szakal;J. Tew
中科院分区：
文献类型：
--
作者：
Y. X. Schwarz;M. Yang;D. Qin;J. Wu;W. Jarvis;S. Grant;G. F. Burton;A. Szakal;J. Tew
滤泡树突状细胞 (FDC) 减少 B 细胞凋亡的观察结果提出了这样的假设：FDC 可能通过保护恶性 B 细胞免于凋亡性死亡来增强肿瘤细胞的存活。为了验证这一观点，在存在或不存在 FDC 的情况下，通过抗 Fas 或各种抗肿瘤药物诱导 B 细胞淋巴瘤发生细胞凋亡。通过TUNEL 分析检测和量化细胞凋亡。当FDC与B细胞的比例≥1:16时，FDC显着拮抗抗Fas、依托泊苷、环磷酰胺和白消安诱导的细胞凋亡。例如，用 10 ng/ml 抗 Fas 处理导致 60-90% 的 A20 细胞在 6 小时内发生凋亡，而添加 FDC 将细胞凋亡降低至背景水平 (3-15%)。同样，白消安治疗诱导 55-80% 的 A20 细胞凋亡，而添加 FDC 将 B 细胞死亡减少至 </=15%；此外，FDC 耗尽会导致保护作用失效。相反，FDC 不会逆转阿霉素的细胞凋亡诱导作用。阻断抗 Fas 或白消安诱导的细胞凋亡的能力不仅限于 A20，还在其他四种恶性前 B 细胞或 B 细胞系中观察到。 FDC 使恶性 B 细胞免于凋亡的机制不涉及 Bcl-2、Bcl-XL 或 Bax 水平的改变。总的来说，这些数据提出了 FDC 可能通过保护恶性 B 细胞免受抗 Fas 和一些但不是所有化疗药物诱导的细胞凋亡来增强肿瘤细胞存活的可能性。
The observation that follicular dendritic cells (FDC) reduce apoptosis in B cells prompted the hypothesis that FDC might enhance tumor cell survival by protecting malignant B cells from apoptotic death. To test this notion, apoptosis was induced in B cell lymphomas by anti-Fas or various antineoplastic agents in the presence and absence of FDC. Apoptosis was detected and quantified by TUNEL analysis. Induction of apoptosis with anti-Fas, etoposide, cyclophosphamide, and busulfan was markedly antagonized by FDC at FDC to B cell ratios of >/=1:16. For example, treatment with 10 ng/ml anti-Fas caused 60-90% of A20 cells to undergo apoptosis in 6 h, whereas addition of FDC reduced apoptosis to background levels (3-15%). Similarly, treatment with busulfan induced apoptosis in 55-80% of A20 cells, whereas addition of FDC reduced B cell death to </=15%; moreover, depletion of FDC abrogated the protective actions. In contrast, the apoptosis-inducing effect of Adriamycin was not reversed by FDC. The ability to block apoptosis induced by anti-Fas or busulfan was not limited to A20 but was observed in four other malignant pre-B cell or B cell lines. The mechanism by which FDC spare malignant B cells from apoptosis did not involve alterations in levels of Bcl-2, Bcl-XL, or Bax. Collectively, these data raise the possibility that FDC may enhance tumor cell survival by protecting malignant B cells against apoptosis induced by anti-Fas and some but not all chemotherapeutic agents.