Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type IFN
Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type IFN
复制标题
DOI：
10.4049/jimmunol.174.7.4043
复制
发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Hartmann, G
中科院分区：
文献类型：
--
作者：
Bekeredjian-Ding, IB;Wagner, M;Hartmann, G
通过 TILL 获得的人类 B 细胞激活的详细信息可能有助于更好地了解 B 细胞参与自身免疫和恶性肿瘤的过程。在这项研究中，我们发现了 TLR7 和 TLR9 介导的 B 细胞刺激调节的根本区别：虽然 TLR7 配体雷西莫德 (R848) 和洛索立宾诱导多克隆幼稚 13 细胞增殖需要浆细胞样树突状细胞 (I'DC) 的存在，但通过 TLR9 配体 CpG 的激活与 PDC 无关。我们发现PDC衍生的I型IFN通过选择性上调TLR7表达来增强B细胞的TLR7敏感性。相反，TLR9 和其他研究的 TLR 的表达水平保持不变。在 I 型 IFN 存在的情况下，TLR7 连接引发多克隆 B 细胞扩增和 B 细胞向产生 Ig 的浆细胞分化；值得注意的是，这种情况的发生与 T 细胞帮助和 B 细胞 Ag 无关。在有或没有 I 型 IFN 的情况下，人 B 细胞对其他 TLR 的配体（包括 TLR2、rLR4 和 TLR6）均没有反应。总之，我们的结果揭示了人类 B 细胞中 TLR7 和 TLR9 功能的独特调节，并强调 TLR7 和 TLR9 作为 B 细胞介导的免疫和疾病治疗干预的独特靶点。
Detailed information of human B cell activation via TILL may lead to a better understanding of B cell involvement in autoimmunity and malignancy. In this stndy we identified a fundamental difference in the regulation of TLR7- and TLR9-mediated B cell stimulation: whereas the induction of polyclonal naive 13 cell proliferation by the TLR7 ligands resiquimod (R848) and loxoribine required the presence of plasmacytoid dendritic cells (I'DCs), activation via the TLR9 ligand CpG was independent of PDCs. We found that PDC-derived type I IFN enhanced TLR7 serlsitivity of B cells by selectively up-regulating TLR7 expression. In contrast the expression levels of TLR9 and of other TLRs studied remained unchanged. In the presence of type I IFN, TLR7 ligation triggered polyclonal B cell expansion and B cell differentiation toward Ig-producing plasma cells; notably, this occurred independently of T cell help and B cell Ag. Human B cells did not respond to ligands of other TLRs including TLR2,,rLR4 and TLR6 with and without type I IFN. In conclusion, our results reveal a distinct regulation of TLR7 and TLR9 function in human B cells and highlight TLR7 and TLR9 as unique targets for therapeutic intervention in B cell-mediated immunity and disease.