Follicular Dendritic Cells Protect Malignant B Cells from Apoptosis Induced by Anti-Fas and Antineoplastic Agents

Abstract

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.