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| Content Provider | frontiers |
|---|---|
| Author | Cheng, Liang Li, Guangming Pellegry, Caroline Marnata Yasui, Fumihiko Li, Feng Zurawski, Sandra M. Zurawski, Gerard Levy, Yves Ting, Jenny P.-Y. Su, Lishan |
| Abstract | Mice 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. |
| ISSN | 16643224 |
| DOI | 10.3389/fimmu.2021.672143 |
| Volume Number | 12 |
| Journal | Frontiers in Immunology |
| Language | English |
| Publisher Date | 2021-05-18 |
| Access Restriction | Open |
| Subject Keyword | CpG-B IgG induction Plasmacytoid dendritic cell Immunoglobin class-switch CD40-targeting vaccination IFN-alpha B cell maturation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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