Human and rhesus plasmacytoid dendritic cell and B-cell responses to Toll-like receptor stimulation

Immunology. 2011 Nov;134(3):257-69. doi: 10.1111/j.1365-2567.2011.03484.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD20 / immunology
  • Antigens, CD20 / metabolism
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Imidazoles / pharmacology
  • Immunoglobulin M / immunology
  • Immunoglobulin M / metabolism
  • Interferon-alpha / immunology*
  • Interferon-alpha / metabolism
  • Interferon-alpha / pharmacology
  • Macaca mulatta / immunology*
  • Macaca mulatta / metabolism
  • Oligodeoxyribonucleotides / pharmacology
  • Quinolines / pharmacology
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 8 / agonists
  • Toll-Like Receptor 8 / immunology
  • Toll-Like Receptor 8 / metabolism
  • Toll-Like Receptor 9 / agonists
  • Toll-Like Receptor 9 / immunology
  • Toll-Like Receptor 9 / metabolism
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / immunology*
  • Toll-Like Receptors / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism

Substances

  • Antigens, CD20
  • Imidazoles
  • Immunoglobulin M
  • Interferon-alpha
  • Oligodeoxyribonucleotides
  • Quinolines
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • Tumor Necrosis Factor Receptor Superfamily, Member 7