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Human and rhesus plasmacytoid dendritic cell and B-cell responses to Toll-like receptor stimulation.
Immunology. 2011 Nov; 134(3):257-69.I

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+Show Affiliations

Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21977996

Citation

Gujer, Cornelia, et al. "Human and Rhesus Plasmacytoid Dendritic Cell and B-cell Responses to Toll-like Receptor Stimulation." Immunology, vol. 134, no. 3, 2011, pp. 257-69.
Gujer C, Sundling C, Seder RA, et al. Human and rhesus plasmacytoid dendritic cell and B-cell responses to Toll-like receptor stimulation. Immunology. 2011;134(3):257-69.
Gujer, C., Sundling, C., Seder, R. A., Karlsson Hedestam, G. B., & Loré, K. (2011). Human and rhesus plasmacytoid dendritic cell and B-cell responses to Toll-like receptor stimulation. Immunology, 134(3), 257-69. https://doi.org/10.1111/j.1365-2567.2011.03484.x
Gujer C, et al. Human and Rhesus Plasmacytoid Dendritic Cell and B-cell Responses to Toll-like Receptor Stimulation. Immunology. 2011;134(3):257-69. PubMed PMID: 21977996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human and rhesus plasmacytoid dendritic cell and B-cell responses to Toll-like receptor stimulation. AU - Gujer,Cornelia, AU - Sundling,Christopher, AU - Seder,Robert A, AU - Karlsson Hedestam,Gunilla B, AU - Loré,Karin, PY - 2011/10/8/entrez PY - 2011/10/8/pubmed PY - 2011/12/14/medline SP - 257 EP - 69 JF - Immunology JO - Immunology VL - 134 IS - 3 N2 - 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. SN - 1365-2567 UR - https://www.unboundmedicine.com/medline/citation/21977996/Human_and_rhesus_plasmacytoid_dendritic_cell_and_B_cell_responses_to_Toll_like_receptor_stimulation_ L2 - https://doi.org/10.1111/j.1365-2567.2011.03484.x DB - PRIME DP - Unbound Medicine ER -