title: Human and rhesus plasmacytoid dendritic cell and B-cell responses to Toll-like receptor stimulation.
abstract: Interferon-α (IFN-α) produced at high levels by human plasmacytoid dendritic cells (pDCs) can specifically regulate B-cell activation to Toll-like receptor (TLR) 7/8 stimulation. To explore the influence of IFN-α and pDCs on B-cell functions in vivo, studies in non-human primates that closely resemble humans in terms of TLR expression on different subsets of immune cells are valuable. Here, we performed a side-by side comparison of the response pattern between human and rhesus macaque B cells and pDCs in vitro to well-defined TLR ligands and tested whether IFN-α enhanced B-cell function comparably. We found that both human and rhesus B cells proliferated while pDCs from both species produced high levels of IFN-α in response to ligands targeting TLR7/8 and TLR9. Both human and rhesus B-cell proliferation to TLR7/8 ligand and CpG class C was significantly increased in the presence of IFN-α. Although both human and rhesus B cells produced IgM upon stimulation, only human B cells acquired high expression of CD27 associated with plasmablast formation. Instead, rhesus B-cell differentiation and IgM levels correlated to down-regulation of CD20. These data suggest that the response pattern of human and rhesus B cells and pDCs to TLR7/8 and TLR9 is similar, although some differences in the cell surface phenotype of the differentiating cells exist. A more thorough understanding of potential similarities and differences between human and rhesus cells and their response to potential vaccine components will provide important information for translating non-human primate studies into human trials.
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Cornelia
authors: C
authors: Gujer
authors: Christopher
authors: C
authors: Sundling
authors: Robert A
authors: RA
authors: Seder
authors: Gunilla B
authors: GB
authors: Karlsson Hedestam
authors: Karin
authors: K
authors: Loré
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D016898:Interferon-alpha / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008253:Macaca mulatta / Q000276:immunology* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism
chemical_list: D018951:Antigens, CD20; D007093:Imidazoles; D007075:Immunoglobulin M; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D011804:Quinolines; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7