title: Toll-like receptor agonists synergistically increase proliferation and activation of B cells by epstein-barr virus.
abstract: Epstein-Barr virus (EBV) efficiently drives proliferation of human primary B cells in vitro, a process relevant for human diseases such as infectious mononucleosis and posttransplant lymphoproliferative disease. Human B-cell proliferation is also driven by ligands of Toll-like receptors (TLRs), notably viral or bacterial DNA containing unmethylated CpG dinucleotides, which triggers TLR9. Here we quantitatively investigated how TLR stimuli influence EBV-driven B-cell proliferation and expression of effector molecules. CpG DNA synergistically increased EBV-driven proliferation and transformation, T-cell costimulatory molecules, and early production of interleukin-6. CpG DNA alone activated only memory B cells, but CpG DNA enhanced EBV-mediated transformation of both memory and naive B cells. Ligands for TLR2 or TLR7/8 or whole bacteria had a weaker but still superadditive effect on B-cell transformation. Additionally, CpG DNA facilitated the release of transforming virus by established EBV-infected lymphoblastoid cell lines. These results suggest that the proliferation of EBV-infected B cells and their capability to interact with immune effector cells may be directly influenced by components of bacteria or other microbes present at the site of infection.
authors.affiliation: Helmholtz-Zentrum München, Marchioninistr. 25, 81377 Munich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Iskra
authors.forename: Markus
authors.initials: M
authors.lastname: Kalla
authors.forename: Henri-Jacques
authors.initials: HJ
authors.lastname: Delecluse
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hammerschmidt
authors.forename: Andreas
authors.initials: A
authors.lastname: Moosmann
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists* / Q000502:physiology; D017735:Virus Latency
chemical_list: C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051193:Toll-Like Receptors