TLR-mediated stimulation of APC: Distinct cytokine responses of B cells and dendritic cells.

TLR-mediated stimulation of APC: Distinct cytokine responses of B cells and dendritic cells.
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DOI:
10.1002/eji.200636483
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发表时间:
2007-11
影响因子:
5.4
通讯作者:
Gray, David
Gray, David
中科院分区:
医学3区
文献类型:
--
作者:
Barr, Tom A;Brown, Sheila;Ryan, Gemma;Zhao, Jiexin;Gray, David

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除了在体液免疫中的作用外,B淋巴细胞还是重要的抗原呈递细胞(APC)。以与其他APC相同的方式,B细胞在活化后产生细胞因子,并具有调节T细胞应答的潜力。在这项研究中,我们调查了哪些小鼠B细胞亚群是最有效的细胞因子产生者,并检查了Toll样受体(TLR)在控制B细胞分泌IL-6、IL-10、IL-12和IFN-γ中的作用。某些细胞因子的产生仅限于特定的亚群。脾脏边缘带和B1细胞是B细胞IL-10的主要来源。相反,发现滤泡B细胞直接离体表达IFN-γ mRNA。激活刺激的性质显著影响B细胞产生的细胞因子。因此,响应于组合的TLR刺激,或通过佛波醇酯,分泌IFN-γ。IL-10是通过TLR 2、4或9的T依赖性激活或刺激引起的。这种细胞因子表达模式与树突状细胞引起的形成对比。QRT-PCR阵列数据表明,这可能是由于TLR信号分子、效应子和衔接子的差异表达。我们的数据突出了当B细胞作为APC时免疫调节的潜在独特性质。
In addition to their role in humoral immunity, B lymphocytes are important antigen-presenting cells (APC). In the same way as other APC, B cells make cytokines upon activation and have the potential to modulate T cell responses. In this study, we investigated which mouse B cell subsets are the most potent cytokine producers, and examined the role of Toll-like receptors (TLR) in the control of secretion of IL-6, IL-10, IL-12 and IFN-γ by B cells. Production of some cytokines was restricted to particular subsets. Marginal zone and B1 cells were the predominant source of B cell IL-10 in the spleen. Conversely, follicular B cells were found to express IFN-γ mRNA directly ex vivo. The nature of the activating stimulus dramatically influenced the cytokine made by B cells. Thus, in response to combined TLR stimulation, or via phorbol esters, IFN-γ was secreted. IL-10 was elicited by T-dependent activation or stimulation through TLR2, 4 or 9. This pattern of cytokine expression contrasts with that elicited from dendritic cells. QRT-PCR array data indicate that this may be due to differential expression of TLR signalling molecules, effectors and adaptors. Our data highlight the potentially unique nature of immune modulation when B cells act as APC.