Human B Cell Responses to TLR Ligands Are Differentially Modulated by Myeloid and Plasmacytoid Dendritic Cells
Human B Cell Responses to TLR Ligands Are Differentially Modulated by Myeloid and Plasmacytoid Dendritic Cells
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DOI：
10.4049/jimmunol.0802257
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发表时间：
2009-02-15
影响因子：
4.4
通讯作者：
Lore, Karin
中科院分区：
文献类型：
--
作者：
Douagi, Iyadh;Gujer, Cornelia;Lore, Karin
选择的TLR配体作为疫苗佐剂正在评估中，并且已知其活化树突细胞（DC）和B细胞以影响疫苗诱导的Ab应答。然而，两种主要的人DC亚群，髓样（MDC）和浆细胞样（PDC），在支持B细胞对TLR配体的应答中的相对贡献仍然知之甚少。我们发现PDCs而不是MDCs显著增强了B细胞对TLR 7/8-L（一种咪唑喹啉衍生物）的增殖反应，并在较小程度上增强了对TLR 9配体（CpG ODN A、B和C类）的增殖反应。PDCs强烈增强TLR 7/8-L诱导的记忆和幼稚B细胞的增殖，但仅能够支持记忆细胞分化为CD 27（高）浆母细胞。在TLR 7/8刺激下，PDCs介导了转录因子B淋巴细胞诱导成熟蛋白1和X盒结合蛋白1的上调，并增强了B细胞向IgM-、IgG-和IgA-产生细胞的分化。由PDCs产生的高水平的I型IFN是对TLR 7/8刺激的作用的主要介质。尽管MDCs对TLR 7/8刺激的应答中表达较高水平的已知B细胞生长因子IL-6、IL-10和B细胞活化因子，但它们不能增强该系统中的B细胞应答。这些数据有助于解释PDC和MDC在调节人B细胞应答中的不同作用，并有助于选择特异性TLR配体作为疫苗佐剂。免疫学杂志，2009，182：1991-2001。
Selected TLR ligands are under evaluation as vaccine adjuvants and are known to activate dendritic cells (DCs) and B cells to affect vaccine-induced Ab responses. However, the relative contribution of the two main human DC subsets, myeloid (MDCs) and plasmacytoid (PDCs), in supporting B cell responses to TLR ligands remains poorly understood. We found that PDCs but not MDCs markedly enhanced B cell proliferation in response to TLR7/8-L, an imidazoquinoline derivative, and to a lesser extent to TLR9 ligands (CpG ODN classes A, B, and C). PDCs strongly enhanced TLR7/8-L-induced proliferation of both memory and naive B cells but were only able to support memory cells to differentiate to CD27(high) plasmablasts. In response to TLR7/8 stimulation, PDCs mediated the up-regulation of transcription factors B lymphocyte-induced maturation protein 1 and X-box binding protein 1 and enhanced differentiation of B cells into IgM-, IgG-, and IgA-producing cells. Type I IFN produced to high levels by PDCs was the principal mediator of the effects on TLR7/8 stimulation. Although MDCs expressed higher levels of the known B cell growth factors IL-6, IL-10, and B cell-activating factor in response to TLR7/8 stimulation, they were unable to enhance B cell responses in this system. These data help decipher the different roles of PDCs and MDCs for modulating human B cell responses and can contribute to selection of specific TLR ligands as vaccine adjuvants. The Journal of Immunology, 2009, 182: 1991-2001.