Cellular and molecular basis of Ag-specific and Ag-nonspecific T-dependent antibody responses in vivo (IRC8P.447)

Abstract

Abstract Although B7 is essential for T-dependent Ag-specific Ab production, little is known about cell type specific role of B7 for these responses. Utilizing B7cKO mice, the cell type specific roles of B7 costimulation 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 (BC-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 BC-B7KO showed reduction of total number of GC B and TFH despite normal numbers of NP-binding GC B. These results demonstrate that B7 on DC but not B cells is critical for Ag-specific CD4+ T cell expansion and IgG1 production. In contrast, a distinct pathway dependent upon B7 on B cells but not DC supported apparently Ag-nonspecific GC response. Of interest, MHCII on B cells but not on DC was required for Ag-nonspecific GC response, indicating that cognate T-B but not T-DC interaction was responsible for eliciting Ag-nonspecific GC response. Our study revealed a previously unappreciated B7-dependent Ag-nonspecific Ab production pathway and demonstrated distinct cellular and molecular pathways for Ag-specific and Ag-nonspecific components of T-dependent Ab responses.