The use of monoclonal antibodies to deliver antigen (Ag) to dendritic cells (DC) has shown to be a novel immunisation strategy of strong potential for vaccine development. DC are primarily known to support antibody responses by priming CD4+ T cells and contributing for the generation of T follicular helper cells (TFH), which support B cell proliferation and differentiation into antibody-secreting cells. In contrast to CD4+ T cells that can only recognise linear peptide epitopes presented on MHC II; B cells recognise antigen in their native form. It is becoming increasingly clear that DC not only contribute to humoral immunity by activating CD4+ T cells, but also by directly priming B cells. Targeting Ag to Clec9A has been long known to induce potent humoral responses even in the absence of adjuvants. We have previously shown that Clec9A-targeting induces potent TFH responses. We now show that the same immunisation strategy not only contributes for efficient presentation of antigen on MHCII by cDC1, but also allows for the retention of native antigen on their surface. With the use of in vivo imaging, we have observed that display of native antigen on cDC1 facilitates a direct interaction between them and Ag-specific B cells in regions bordering B cell follicles in the lymph-node and spleen. cDC1 native Ag presentation to B cells enables an efficient B cell activation and migration to the T/B border for MHCII restricted Ag-presentation to TFH for acquisition of help. Interestingly, we have also observed that MHCII-restricted presentation by B cells to TFH further supports the latest. These findings suggest that Clec9A-targeting represents an efficient mechanism for B cell activation and generation of humoral immunity, which can be exploited by novel vaccination approaches.