Poeck Hendrik, Wagner Moritz, Battiany Julia, Rothenfusser Simon, Wellisch Daniela, Hornung Veit, Jahrsdorfer Bernd, Giese Thomas, Endres Stefan, Hartmann Gunther
Department of Internal Medicine, Division of Clinical Pharmacology, Ludwig-Maximilians-University of Munich, Germany.
Blood. 2004 Apr 15;103(8):3058-64. doi: 10.1182/blood-2003-08-2972. Epub 2003 Dec 30.
It has been reported that interferon alpha (IFN-alpha) enhances humoral immunity and that dendritic cells of the myeloid lineage promote B-cell differentiation. Here we studied whether the plasmacytoid dendritic cell (PDC), a subset of dendritic cells specialized for the production of IFN-alpha, is involved in regulating B-cell differentiation and immunoglobulin production. The recently identified class of CpG oligonucleotides (CpG-C) was used to activate both B cells and PDCs via Toll-like receptor 9 (TLR9). The presence of PDCs synergistically enhanced CD86 expression, cytokine production (interleukin 6 [IL-6], tumor necrosis factor alpha, and IL-10) and plasma cell differentiation of isolated human peripheral blood B cells stimulated through CpG-C and B-cell antigen receptor (BCR) ligation. This stimulation protocol was sufficient to drive purified naive B cells into IgM-producing plasma cells and to trigger IgG synthesis in memory B cells. PDCs contributed to B-cell activation via IFN-alpha secretion. Up-regulation of TLR9 on B cells was not involved. These results demonstrate that CpG-stimulated PDCs induce plasma cell differentiation in naive and memory B cells in the absence of T-cell help, providing an explanation for the excellent activity of CpG oligonucleotides as a humoral vaccine adjuvant.
据报道，α干扰素（IFN-α）可增强体液免疫，且髓系谱系的树突状细胞可促进B细胞分化。在此，我们研究了浆细胞样树突状细胞（PDC），即专门产生IFN-α的树突状细胞亚群，是否参与调节B细胞分化和免疫球蛋白产生。最近鉴定出的一类CpG寡核苷酸（CpG-C）被用于通过Toll样受体9（TLR9）激活B细胞和PDC。PDC的存在协同增强了经CpG-C和B细胞抗原受体（BCR）连接刺激的分离人外周血B细胞的CD86表达、细胞因子产生（白细胞介素6 [IL-6]、肿瘤坏死因子α和IL-10）以及浆细胞分化。该刺激方案足以驱使纯化的初始B细胞分化为产生IgM的浆细胞，并触发记忆B细胞中的IgG合成。PDC通过分泌IFN-α促进B细胞活化。B细胞上TLR9的上调未参与其中。这些结果表明，在没有T细胞辅助的情况下，CpG刺激的PDC可诱导初始和记忆B细胞中的浆细胞分化，这为CpG寡核苷酸作为体液疫苗佐剂的卓越活性提供了解释。
