title: Comparative In Vitro Immune Stimulation Analysis of Primary Human B Cells and B Cell Lines.
abstract: B cell specific immunomodulatory drugs still remain an unmet medical need. Utilisation of validated simplified in vitro models would allow readily obtaining new insights in the complexity of B cell regulation. For this purpose we investigated which human B lymphocyte stimulation assays may be ideally suited to investigate new B lymphocyte immunosuppressants. Primary polyclonal human B cells underwent in vitro stimulation and their proliferation, production of immunoglobulins (Igs) and of cytokines, and expression of cell surface molecules were analysed using various stimuli. ODN2006, a toll-like receptor 9 (TLR9) agonist, was the most potent general B cell stimulus. Subsequently, we investigated on which human B cell lines ODN2006 evoked the broadest immunostimulatory effects. The Namalwa cell line proved to be the most responsive upon TLR9 stimulation and hence may serve as a relevant, homogeneous, and stable B cell model in an in vitro phenotypic assay for the discovery of new targets and inhibitors of the B cell activation processes. As for the read-out for such screening assay, it is proposed that the expression of activation and costimulatory surface markers reliably reflects B lymphocyte activation.
authors.affiliation: KU Leuven, Interface Valorisation Platform (IVAP), 3000 Leuven, Belgium; Department of Microbiology & Immunology, Laboratory of Experimental Transplantation, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Kristien
authors.initials: K
authors.lastname: Van Belle
authors.affiliation: KU Leuven, Interface Valorisation Platform (IVAP), 3000 Leuven, Belgium; Department of Microbiology & Immunology, Laboratory of Experimental Transplantation, KU Leuven, 3000 Leuven, Belgium; Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, 3000 Leuven, Belgium.
authors.forename: Jean
authors.initials: J
authors.lastname: Herman
authors.affiliation: Bioceros, 3584 CM Utrecht, Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: KU Leuven, Interface Valorisation Platform (IVAP), 3000 Leuven, Belgium; Department of Microbiology & Immunology, Laboratory of Experimental Transplantation, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Mark
authors.initials: M
authors.lastname: Waer
authors.affiliation: KU Leuven, Interface Valorisation Platform (IVAP), 3000 Leuven, Belgium; Department of Microbiology & Immunology, Laboratory of Experimental Transplantation, KU Leuven, 3000 Leuven, Belgium; Department of Nephrology, University Hospitals Leuven, 3000 Leuven, Belgium.
authors.forename: Ben
authors.identifier: 0000-0003-1314-9675
authors.initials: B
authors.lastname: Sprangers
authors.affiliation: KU Leuven, Interface Valorisation Platform (IVAP), 3000 Leuven, Belgium; Department of Microbiology & Immunology, Laboratory of Experimental Transplantation, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Thierry
authors.identifier: 0000-0002-3920-2916
authors.initials: T
authors.lastname: Louat
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051217:Toll-Like Receptor 9 / Q000819:agonists*
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D008565:Membrane Proteins; C000615642:ODN2006; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9