Dendritic cell-B cell interactions in the marginal zone drive extrafollicular antibody responses. (61.4)

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.