TLR1/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and memory B cell subsets to produce cytokines, chemokines, and hematopoietic growth factors.
TLR1/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and memory B cell subsets to produce cytokines, chemokines, and hematopoietic growth factors.
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DOI：
10.1007/s10875-010-9456-8
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发表时间：
2011-02
影响因子：
9.1
通讯作者：
Gupta, Sudhir
中科院分区：
文献类型：
--
作者：
Agrawal, Sudhanshu;Gupta, Sudhir
最近，据报道，使用多种信号，鼠和人B细胞分泌几种具有促炎和免疫调节特性的细胞因子。我们首次对纯化的人外周血B细胞（CD 19+）和未处理的人外周血淋巴细胞（CD 19+）产生的24种细胞因子、趋化因子和造血生长因子进行了全面分析。（CD 19 + CD 27-）和记忆（CD 19 + CD 27+）B细胞对Toll样受体（TLR）配体Pam 3CSK提供的直接和排他信号的应答（TLR 1/TLR 2）、咪喹莫特（TLR 7）和GpG-ODN 2006（TLR 9）。所有三种TLR配体均刺激B细胞（CD 19+）产生细胞因子IL-1α、IL-1β、IL-6、TNF-α、IL-13和IL-10，以及趋化因子MIP-1α、MIP-1β、MCP-1、IP-10和IL-8。然而，GM-CSF和G-CSF的产生主要由TLR 2激动剂诱导。大多数细胞因子/趋化因子/造血生长因子主要或专门由记忆B细胞产生，并且通常，TLR 2信号比通过TLR 7和TLR 9提供的信号更强。未观察到嗜酸性粒细胞趋化因子、IFN-α、IFN-γ、IL-2、IL-3、IL-4、IL-5、IL-7、IL-15、IL-17、IL-12 p40、IL-12 p70和TNF-β（光氧化物）的显著分泌。这些数据表明，人B细胞可以通过TLR 1/TLR 2、TLR 7和TLR 9直接活化，以诱导细胞因子、趋化因子和造血生长因子的分泌，并表明B细胞在针对微生物发病机制和免疫稳态的免疫应答中的作用。
Recently, it has been reported that using multiple signals, murine and human B cells secrete several cytokines with pro-inflammatory and immunoregulatory properties. We present the first comprehensive analysis of 24 cytokines, chemokines, and hematopoietic growth factors production by purified human peripheral blood B cells (CD19+), and naive (CD19+CD27-) and memory (CD19+CD27+) B cells in response to direct and exclusive signaling provided by toll-like receptor (TLR) ligands Pam3CSK (TLR1/TLR2), Imiquimod (TLR7), and GpG-ODN2006 (TLR9). All three TLR ligands stimulated B cells (CD19+) to produce cytokines IL-1α, IL-1β, IL-6, TNF-α, IL-13, and IL-10, and chemokines MIP-1α, MIP-1β, MCP-1, IP-10, and IL-8. However, GM-CSF and G-CSF production was predominantly induced by TLR2 agonist. Most cytokines/chemokines/hematopoietic growth factors were predominantly or exclusively produced by memory B cells, and in general, TLR2 signal was more powerful than signal provided viaTLR7 and TLR9. No significant secretion of eotaxin, IFN-α, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-7, IL-15, IL-17, IL-12p40, IL-12p70, and TNF-β (lymphotoxin) was observed. These data demonstrate that human B cells can be directly activated viaTLR1/TLR2, TLR7, and TLR9 to induce secretion of cytokines, chemokines, and hematopoietic growth factors and suggest a role of B cells in immune response against microbial pathogenesis and immune homeostasis.
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影响因子：
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