BATF3-deficient mice that lack CD8 dendritic cells (DCs) showed an exacerbation of chronic graft-versus-host disease (cGVHD), including T follicular helper (Tfh) cell and autoantibody responses, whereas mice carrying the lupus-suppressive locus with a mutation in the G-CSFR showed an expansion of CD8 DCs and a poor mobilization of plasmacytoid DCs (pDCs) and responded poorly to cGVHD induction. Here, we investigated the contribution of CD8 DCs and pDCs to the humoral response to protein immunization, where CD8 DCs are thought to represent the major inducers. Both BATF3 and mice had reduced humoral and germinal center (GC) responses compared with C57BL/6 (B6) controls. We showed that B6-derived CD4 DCs are the major early producers of IL-6, followed by CD4CD8 DCs. Surprisingly, IL-6 production and CD80 expression also increased in CD8 DCs after immunization, and B6-derived CD8 DCs rescued Ag-specific adaptive responses in BATF3 mice. In addition, inflammatory pDCs (ipDCs) produced more IL-6 than all conventional DCs combined. Interestingly, G-CSFR is highly expressed on pDCs. G-CSF expanded pDC and CD8 DC numbers and IL-6 production by ipDCs and CD4 DCs, and it improved the quality of Ab response, increasing the localization of Ag-specific T cells to the GC. Finally, G-CSF activated STAT3 in early G-CSFR common lymphoid progenitors of cDCs/pDCs but not in mature cells. In conclusion, we showed a multilayered role of DC subsets in priming Tfh cells in protein immunization, and we unveiled the importance of G-CSFR signaling in the development and function pDCs.