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dc.contributor.authorCheng, Liang
dc.contributor.authorLi, Guangming
dc.contributor.authorPellegry, Caroline Marnata
dc.contributor.authorYasui, Fumihiko
dc.contributor.authorLi, Feng
dc.contributor.authorZurawski, Sandra M
dc.contributor.authorZurawski, Gerard
dc.contributor.authorLevy, Yves
dc.contributor.authorTing, Jenny P-Y
dc.contributor.authorSu, Lishan
dc.date.accessioned2021-06-09T18:10:04Z
dc.date.available2021-06-09T18:10:04Z
dc.date.issued2021-05-18
dc.identifier.urihttp://hdl.handle.net/10713/15966
dc.description.abstractMice reconstituted with a human immune system (humanized mice) provide a robust model to study human immunology, vaccinology, and human infectious diseases. However, the development and function of B cells in humanized mice is impaired. B cells from humanized mice are immature and are impaired in IgM to IgG isotype switch in response to infection or vaccination. In the present study we report that Toll-like receptor 9 (TLR9) agonist CpG-B combined with CD40-targeting vaccination triggered human B cell immunoglobin class-switch from IgM+ to IgG+ B cells in humanized mice. Human B cells from mice vaccinated with CpG-B as adjuvant were more mature in phenotype and produced significant levels of both total IgG and antigen-specific IgG. We found that CpG-B treatment activated human pDCs (plasmacytoid dendritic cells) in vivo to induce interferon-alpha (IFN-α)expression in humanized mice. Pre-depletion of human pDC in vivo abrogated the adjuvant effect of CpG-B. Our results indicate that TLR9 and CD40-targeting vaccination triggers human B cell maturation and immunoglobulin class-switch in a pDC-dependent manner in humanized mice. The findings also shed light on induction of human IgG antibodies in humanized mouse models.en_US
dc.description.urihttps://doi.org/10.3389/fimmu.2021.672143en_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Immunologyen_US
dc.rightsCopyright © 2021 Cheng, Li, Pellegry, Yasui, Li, Zurawski, Zurawski, Levy, Ting and Su.en_US
dc.subjectB cell maturationen_US
dc.subjectCD40-targeting vaccinationen_US
dc.subjectCpG-Ben_US
dc.subjectIFN-alphaen_US
dc.subjectIgG inductionen_US
dc.subjectimmunoglobin class-switchen_US
dc.subjectplasmacytoid dendritic cellen_US
dc.titleTLR9- and CD40-Targeting Vaccination Promotes Human B Cell Maturation and IgG Induction pDC-Dependent Mechanisms in Humanized Miceen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fimmu.2021.672143
dc.identifier.pmid34093572
dc.source.volume12
dc.source.beginpage672143
dc.source.endpage
dc.source.countrySwitzerland


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