Xu Hui, Liew Lip Nyin, Kuo I Chun, Huang Chiung Hui, Goh Denise Li-Meng, Chua Kaw Yan
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Immunology. 2008 Oct;125(2):218-28. doi: 10.1111/j.1365-2567.2008.02832.x. Epub 2008 Mar 18.
Lipopolysaccharide (LPS) is a major component of environmental microbial products. Studies have defined the LPS dose as a critical determining factor in driving differential T-cell polarization but the direct effects of LPS on individual antigen-presenting cells is unknown. Here, we investigated the effects of LPS doses on naive B cells and the subsequent modulatory effects of these LPS-activated B cells on T-cell polarization. The LPS was able to induce a proliferative response starting at a dose of 100 ng/ml and was capable of enhancing antigen internalization at a dose of 1 microg/ml in naive B cells. Following LPS stimulation, up-regulation of the surface markers CD40, CD86, I-Ad, immunoglobulin M, CD54 and interleukin-10 production, accompanied by down-regulation of CD5 and CD184 (CXCR4) were observed in a LPS dose-dependent manner. Low doses (<10 ng/ml) of LPS-activated B cells drove T helper type 2 polarization whereas high doses (>0.1 microg/ml) of LPS-activated B cells resulted in T regulatory type 1 cell polarization. In conclusion, LPS-activated B cells acquire differential modulatory effects on T-cell polarization. Such modulatory effects of B cells are dependent on the stimulation with LPS in a dose-dependent manner. These observations may provide one of the mechanistic explanations for the influence of environmental microbes on the development of allergic diseases.
脂多糖(LPS)是环境微生物产物的主要成分。研究已将LPS剂量定义为驱动T细胞分化极化的关键决定因素,但LPS对单个抗原呈递细胞的直接影响尚不清楚。在此,我们研究了LPS剂量对初始B细胞的影响以及这些LPS激活的B细胞对T细胞极化的后续调节作用。LPS在剂量为100 ng/ml时就能诱导增殖反应,且在剂量为1 μg/ml时能够增强初始B细胞的抗原内化。LPS刺激后,观察到表面标志物CD40、CD86、I-Ad、免疫球蛋白M、CD54和白细胞介素-10的产生上调,同时伴随着CD5和CD184(CXCR4)的下调,且呈LPS剂量依赖性。低剂量(<10 ng/ml)的LPS激活的B细胞促使2型辅助性T细胞极化,而高剂量(>0.1 μg/ml)的LPS激活的B细胞则导致1型调节性T细胞极化。总之,LPS激活的B细胞对T细胞极化具有不同的调节作用。B细胞的这种调节作用以剂量依赖的方式取决于LPS刺激。这些观察结果可能为环境微生物对过敏性疾病发展的影响提供一种机制解释。