Antibody responses initiated by Clec9A-bearing dendritic cells in normal and Batf3−/− mice

Injection of antigens coupled to antibodies against the dendritic cell (DC) surface molecule Clec9A has been shown to produce strongly enhanced antibody responses even without co-administration of adjuvants, via antigen presentation by DC on MHC class II and consequent production of follicular helper T cells. A series of mutant mice were tested to determine the DC subtypes responsible for this MHC II presentation of targeted antigen, compared to presentation of antigen on MHC I. A new clec9A null mouse was developed; these mice did not give enhanced antibody production, confirming the response was dependent on Clec9A-expressing DC. However targeting of antigen to Clec9A in batf3 null mice produced enhanced antibody responses despite the marked reduction in CD8+ DC, the major Clec9A-expressing DC subtype. This was shown to be dependent on efficient MHC II presentation by minor Clec9A-expressing DC subtypes in the environment of the Batf3−/− mice, namely early cells of the CD8 DC lineage and the plasmacytoid-related CD8+ DC subset, but not by plasmacytoid cells themselves. However in normal mice most MHC II presentation of the Clec9A-targeted antigen was by the major CD8+ DC population, the DC also responsible for presentation on MHC I.

► Enhanced antibody responses on targeting antigens to Clec9A are lost in IRF8 null and Clec9A null mice but retained in Batf3 null mice. ► Batf3 null mice retain subsets of Clec9A-bearing DC, including early CD8+ lineage DC. ► In normal mice most MHC II presentation after targeting antigen to Clec9A is due to CD8+ DC. ► Clec9A bearing plasmacytiod DC do not present Clec9A-targeted antigen.