| First Author | Lee MSJ | Year | 2019 |
| Journal | Eur J Immunol | Volume | 49 |
| Issue | 9 | Pages | 1433-1440 |
| PubMed ID | 31087643 | Mgi Jnum | J:281757 |
| Mgi Id | MGI:6379468 | Doi | 10.1002/eji.201848084 |
| Citation | Lee MSJ, et al. (2019) B cell-intrinsic MyD88 signaling controls IFN-gamma-mediated early IgG2c class switching in mice in response to a particulate adjuvant. Eur J Immunol 49(9):1433-1440 |
| abstractText | Adjuvants improve the potency of vaccines, but the modes of action (MOAs) of most adjuvants are largely unknown. TLR-dependent and -independent innate immune signaling through the adaptor molecule MyD88 has been shown to be pivotal to the effects of most adjuvants; however, MyD88's involvement in the TLR-independent MOAs of adjuvants is poorly understood. Here, using the T-dependent antigen NIPOVA and a unique particulate adjuvant called synthetic hemozoin (sHZ), we show that MyD88 is required for early GC formation and enhanced antibody class-switch recombination (CSR) in mice. Using cell-type-specific MyD88 KO mice, we found that IgG2c class switching, but not IgG1 class switching, was controlled by B cell-intrinsic MyD88 signaling. Notably, IFN-gamma produced by various cells including T cells, NK cells, and dendritic cells was the primary cytokine for IgG2c CSR and B-cell intrinsic MyD88 is required for IFN-gamma production. Moreover, IFN-gamma receptor (IFNgammaR) deficiency abolished sHZ-induced IgG2c production, while recombinant IFN-gamma administration successfully rescued IgG2c CSR impairment in mice lacking B-cell intrinsic MyD88. Together, our results show that B cell-intrinsic MyD88 signaling is involved in the MOA of certain particulate adjuvants and this may enhance our specific understanding of how adjuvants and vaccines work. |
