Abstract

Abstract Targeting Ag directly to dendritic cell (DC) subsets through the use of monoclonal antibodies (mAb) is increasingly being employed as a means to generate CD4 and CD8 T cell responses. However, the ability of individual DC subsets to raise primary Ab responses following Ag targeting is not well characterized. Using the hapten 4-hydroxy-3-nitrophenyl (NP) coupled to mAbs that recognize DC-specific DEC205 or DCIR2, we found that MZ-associated DCIR2+ DCs, but not DEC205+ DCs, were able to induce robust T cell- and CD40-dependent anti-NP Ab responses following injection of soluble Ag. Anti-NP Ab responses were restricted to the IgG1 sub-class but failed to either persist over time or undergo affinity maturation, despite the addition of TLR or RLR agonists. Using adoptive transfers with NP-specific B cells, we show that the unique ability of DCIR2+ DCs to induce Ab responses was associated with rapid, MHC class II-independent activation of Ag-specific B cells that occurred specifically upon Ag delivery to DCIR2. Importantly, we found that NP-specific B cells accumulated in MZ-associated bridging channels in close association with CD11c+ cells as early as 24hr following Ag delivery to DCIR2+ DCs. Together, these results reveal a previously unrecognized role for DC-B cell interactions in splenic bridging channels, and provide a novel mechanism for the initiation of T-dependent extrafollicular Ab responses.

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