Abstract
To be effective, protein priming must induce the development of a distinct lineage of CD4+ T cells named T follicular helper (Tfh) cells, which regulate the differentiation of high-affinity memory B cells and long-lived plasma cells. In this context, we tested how adjuvantation with CpG, the Toll-like receptor 9 agonist used in clinics, contributes to antigen-specific T-cell-dependent B-cell responses in vivo. We found that addition of CpG to other vaccine adjuvant increased the differentiation of antigen-specific Tfh cells without changing the overall magnitude of the T-cell response. This phenomenon correlated with an enhancement of the germinal centre reaction, antigen-specific plasma cells and circulating antibodies. We comprehensively demonstrated that, in addition to the classical Tfh-cell differentiation mediated by conventional DC, the promoting effect due to CpG was orchestrated in vivo by antigen presentation and IL-6 secreted by monocyte-derived dendritic cells (DC) as shown in their absence. Thus, while conventional DC initiate T-cell responses, targeting monocyte-derived DC specifically enhances the Tfh programme needed to regulate high-affinity B-cell protection in vivo.
Highlights
Most vaccines are designed empirically using attenuated pathogens as the source of foreign antigens (Ag)
The T follicular helper (Tfh) enhancing phenomenon was correlated with no difference in the nature of Ag-presenting dendritic cells (DC) or an increase in DC recruited to the draining LN (dLN) after immunisation
We have shown that CpG-B directly acts on monocyte-derived DC (moDC) by inducing IL-6 production that, in turn, enhances Ag-specific Tfh-cell development and, germinal centre (GC)-B-cell reaction and IgG response
Summary
Most vaccines are designed empirically using attenuated pathogens as the source of foreign antigens (Ag). Using three Ag models for which we have direct access in wild-type (WT) mice to antigen (Ag)-specific T cells, Ag-specific B cells and Ag-presenting DC, we document that the adjuvantation with CpG-B of other vaccine adjuvant enhances Ag-specific Tfh cells without changing the overall extent of the Ag-specific T-cell pool. It enhances Ag-specific memory B-cell development and Ab response. These results suggest that targeting moDC can imprint the specialised programme of effector Tfh function needed to promote high-affinity B-cell immunity in vivo that, boosts protein vaccine efficacy
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