CD8α+ dendritic cells (DCs) are best known for their ability to crosspresent antigens to CD8+ T cells but their capacity to induce B cell responses is not widely appreciated. We have previously shown that targeted delivery of antigen to CD8α+ DCs via Clec9A induces strong humoral responses without adjuvant. Here we show that this vaccination strategy fosters direct interactions between CD8α+ DC and antigen-specific B cells.
The contribution of DC-B cell interactions to humoral responses was assessed by examining the antibody response to the B cell hapten NP conjugated to mAb against Clec9A, which, being rat IgG2a, carry effective helper T cell epitopes in mice. The potency of the anti-NP response induced by Clec9A targeting was lost when NP was instead conjugated to non-targeted isotype control mAb, even if helper T cell epitopes were delivered to Clec9A. Thus direct interactions between CD8α+ DC and NP-specific B cells contributed to induction of the anti-NP response. We then used OVA as a model protein antigen to reveal that protein antigens can be efficiently displayed and retained on the surface of CD8α+ DCs. This allowed efficient activation of antigen-specific B cells in a T cell independent manner, resulting in their accumulation along the T-B boarder within 12h of immunization. In contrast, antigen targeted to DEC205, a receptor also expressed on CD8α+ DCs, did not strongly activate antigen-specific B cells and only weakly induced antibody responses. A broader expression pattern of DEC205 by cells other than CD8α+ DCs compared to Clec9A appears to be at least partly responsible for inability to induce B cell activation.
In summary, we identified an important CD8a+ DC-B cell interaction mediated by Clec9A-targeted antigen that facilitates effective B cell activation and may be exploited in the development of next generation vaccines.