title: 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.
authors.affiliation: Department of Microbiology and Immunology, Division of Immunobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond 23298, USA.
authors.forename: Y X
authors.initials: YX
authors.lastname: Schwarz
authors.forename: M y
authors.initials: My
authors.lastname: Yang
authors.forename: D
authors.initials: D
authors.lastname: Qin
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: W D
authors.initials: WD
authors.lastname: Jarvis
authors.forename: S
authors.initials: S
authors.lastname: Grant
authors.forename: G F
authors.initials: GF
authors.lastname: Burton
authors.forename: A K
authors.initials: AK
authors.lastname: Szakal
authors.forename: J G
authors.initials: JG
authors.lastname: Tew
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002469:Cell Separation; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000378:metabolism; D013234:Stem Cells / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor