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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen-specific B cells induces enhanced CD4 + T helper type 1 subset differentiation
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Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen-specific B cells induces enhanced CD4 + T helper type 1 subset differentiation

机译：抗原特异性B细胞对候选类风湿关节炎自身抗原聚集蛋白聚糖的诱导可增强CD4 + T辅助1型亚群的分化

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摘要

Effective immune responses require antigen uptake by antigen-presenting cells (APC), followed by controlled endocytic proteolysis resulting in the generation of antigen-derived peptide fragments that associate with intracellular MHC class II molecules. The resultant peptide-MHC class II complexes then move to the APC surface where they activate CD4 + T cells. Dendritic cells (DC), macrophages and B cells act as efficient APC. In many settings, including the T helper type 1 (Th1) -dependent, proteoglycan-induced arthritis model of rheumatoid arthritis, accumulating evidence demonstrates that antigen presentation by B cells is required for optimal CD4 + T cell activation. The reasons behind this however, remain unclear. In this study we have compared the activation of CD4 + T cells specific for the proteoglycan aggrecan following antigen presentation by DC, macrophages and B cells. We show that aggrecan-specific B cells are equally efficient APC as DC and macrophages and use similar intracellular antigen-processing pathways. Importantly, we also show that antigen presentation by aggrecan-specific B cells to TCR transgenic CD4 + T cells results in enhanced CD4 + T cell interferon-γ production and Th1 effector sub-set differentiation compared with that seen with DC. We conclude that preferential CD4 + Th1 differentiation may define the requirement for B cell APC function in both proteoglycan-induced arthritis and rheumatoid arthritis.
机译：有效的免疫反应需要抗原呈递细胞（APC）吸收抗原，然后进行受控的胞吞蛋白水解作用，从而产生与细胞内MHC II类分子缔合的抗原衍生肽片段。然后，所得的肽-MHC II类复合物移至APC表面，在那里它们激活CD4 + T细胞。树突状细胞（DC），巨噬细胞和B细胞可作为有效的APC。在许多环境中，包括类风湿性关节炎的T辅助1型（Th1）依赖性蛋白聚糖诱导的关节炎模型，越来越多的证据表明B细胞的抗原呈递是CD4 + T细胞最佳活化所必需的。然而，其背后的原因尚不清楚。在这项研究中，我们比较了DC，巨噬细胞和B细胞呈递抗原后蛋白聚糖聚集蛋白聚糖特异的CD4 + T细胞的活化。我们显示，聚集蛋白聚糖特异性B细胞与DC和巨噬细胞一样有效，并且使用相似的细胞内抗原加工途径。重要的是，我们还显示，与DC相比，聚集蛋白聚糖特异性B细胞向TCR转基因CD4 + T细胞呈递抗原会导致CD4 + T细胞干扰素-γ的产生和Th1效应子亚群的分化。我们得出的结论是，优先CD4 + Th1分化可能会定义蛋白聚糖诱导的关节炎和类风湿关节炎中B细胞APC功能的需求。

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