title: Monocyte-derived dendritic cells promote T follicular helper cell differentiation.
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.
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
authors.forename: Svetoslav
authors.initials: S
authors.lastname: Chakarov
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fazilleau
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000097:blood; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000502:physiology*; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; C408982:CPG-oligonucleotide; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D051193:Toll-Like Receptors; D010047:Ovalbumin
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