Cell type specific role of B7 for Ag-specific T and B cell activation and differentiation in T-dependent antibody response in vivo (P1017)

Abstract

Abstract B7.1/B7.2 molecules are essential for eliciting immune responses through CD28-mediated T cell activation, as well as for CTLA-4-mediated negative regulation of T cell responses. Although many cell types (DC, MΦ, B and T) express B7 in vivo, the role of B7 on each cell type is not well defined. Utilizing cell type-specific B7cKO mice, cell type specific roles of B7 for T-dependent GC and Ab responses were analyzed. Upon NP-OVA/Alum immunization, NP-specific IgG1 production was profoundly defective in mice lacking B7 expression on DC (DC-B7KO) but was intact in mice lacking B7 on B cells (B-B7KO). Consistent with this, NP-binding GC B cells and Ag-specific CD4+ T cell expansion were not observed in DC-B7KO. Surprisingly, however, GC formation and total numbers of GC B and TFH were undiminished in DC-B7KO; whereas B-B7KO showed reduction of total number of GC B and TFH despite normal number of NP-binding GC B. In addition, NP-specific secondary Ab was absent in DC-B7KO but intact in B-B7KO. These results clearly demonstrate that B7 on DC but not B cells is critical for Ag-specific CD4+ T cell expansion and IgG1 production as well as for secondary Ab responses. In contrast, a distinct pathway dependent upon B7 on B cells but not DC supports apparently Ag-nonspecific GC response. Further studies are ongoing to evaluate cell type-specific roles of B7 for affinity maturation, memory T/B formation, and potentially nonspecific or autoreactive components during T-dependent Ab response.