TACI-BLyS signaling via B-cell–dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo

Abstract

We demonstrated that B-cell–dendritic cell (DC) interactions via transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) and B-lymphocyte stimulator (BLyS) provide an early signal critical to generate adequate numbers of mature antigen presenting cells (APCs) to prime naive CD8⁺ T cells (CTLs) in vivo. Evidence that B cells are required for efficient CTL generation in mice and that reconstitution with wild-type but not TACI-knockout B cells restored normal CTL responses support our conclusion. Moreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracellular domain of TACI (amino acid [aa] 1-126) restored CTL priming in B-cell–deficient mice in vivo and induced DC maturation in vitro. In fact, following interactions with B cells, splenic DCs rapidly express the CD86 costimulatory molecule, to an extent comparable to the exposure to antigenic stimuli. BLyS^high peptide-pulsed bone marrow–derived DCs, used as vaccines in vivo, cannot generate CTLs in B-cell–deficient and TACI-deficient mice, strongly supporting a need for B-cell–DC cooperation through TACI-BLyS during CTL first encounter with antigens in vivo.