Selective induction of robust antibody responses following antigen targeting to dendritic cell subsets (90.34)

Abstract

Abstract Dendritic cells (DCs) are essential for the initiation and regulation of immune responses. CD8α+ DCs in the mouse spleen express DEC-205 (CD205), while many splenic CD8α- DCs express DC-inhibitory receptor-2 (DCIR2/33D1). Delivering antigen (Ag) via mAbs to either DEC-205 or DCIR2 was shown by other groups to preferentially induce CD8+ and CD4+ T cell responses, respectively. However, the ability of these two DC subsets to induce primary Ab responses is not well defined. Using the conventional hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to mAbs that recognize DEC-205 or DCIR2, we demonstrate that DCIR2+ DCs, but not DEC-205+ DCs, are able to induce robust anti-NP Ab responses following intravenous injection of soluble Ag. These Ab responses were restricted to the IgG1 subclass with little to no IgM or IgG2a production. Surprisingly, the DCIR2-induced Ab response did not require the addition of conventional adjuvants. These responses were both TCR and CD40-dependent, indicating that T-B cell collaboration is required. Finally, we found that CD22 expression by B cells was also required for IgG1 anti-NP responses, suggesting that DC-B cell interactions may be important during early B cell priming via this route of administration. Together these results demonstrate that, similar to the selective priming of T cells by these DC subsets, DCs are also specially equipped to selectively prime B cells and Ab responses. This project was supported in part by NAIAD training grant T32AI007411 and by NIH grant AI52203 and does not necessarily represent the official views of the NAIAD or the NIH.