Diaz-de-Durana Yaiza, Mantchev George T, Bram Richard J, Franco Alessandra
Torrey Pines Institute for Molecular Studies, San Diego, CA, USA.
Blood. 2006 Jan 15;107(2):594-601. doi: 10.1182/blood-2004-12-4708. Epub 2005 Sep 29.
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.
我们证明，通过跨膜激活剂、钙调蛋白和亲环素配体（CAML）相互作用分子（TACI）和B淋巴细胞刺激因子（BLyS）介导的B细胞与树突状细胞（DC）的相互作用提供了一个早期信号，这一信号对于在体内产生足够数量的成熟抗原呈递细胞（APC）以启动初始CD8(+) T细胞（CTL）至关重要。小鼠中高效产生CTL需要B细胞参与，以及用野生型而非TACI基因敲除的B细胞进行重建可恢复正常CTL反应的证据支持了我们的结论。此外，低剂量表达TACI胞外结构域（氨基酸[aa] 1-126）的TACI融合蛋白（TACI-Fc）在体内恢复了B细胞缺陷小鼠的CTL启动，并在体外诱导了DC成熟。事实上，与B细胞相互作用后，脾DC迅速表达共刺激分子CD86，其程度与暴露于抗原刺激相当。体内用作疫苗的BLyS(高)肽脉冲骨髓来源的DC在B细胞缺陷和TACI缺陷小鼠中不能产生CTL，这有力地支持了在体内CTL首次遇到抗原时，需要通过TACI-BLyS进行B细胞-DC合作。
