Tan Jiufeng, Jin Xuefei, Zhao Rui, Wei Xin, Liu Yan, Kong Xiangbo
Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Department of Otolaryngology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Oncol Rep. 2015 Mar;33(3):1512-8. doi: 10.3892/or.2014.3684. Epub 2014 Dec 19.
Prostate cancer is the most common malignancy in males and easily develops to be aggressive which is closely related to the chronic inflammatory tumor microenvironment in situ. This study aimed to assess the immunoglobulin G (IgG) subclass of B cells and explore their interactions with T follicular helper (Tfh) subsets in prostate cancer patients. The percentages of peripheral blood naïve B cells, memory B cells and mature B cells, as well as Tfh1, Tfh2 and Tfh17 cells were analyzed or sorted by FACSAria. The ratios of the different IgG subclasses (IgG1, IgG2, IgG3 and IgG4) were detected by ELISA, and the expression levels of CXCR3 and CCR6 were measured using RT-PCR and western blot analysis. Meanwhile a co-culture system of B and Tfh cells was to assess the effect of each Tfh subset on the antibody subclass switching of B cells in vitro. We observed higher percentages of 3 Tfh subsets and IgG4+ B cells in the patients with prostate cancer than that in the health controls and proved a positive correlation between Tfh2 and IgG4+ B cells. Then we verified that IL-4, IL-6, IL-10 and prostaglandin E2 (PGE2) effectively promoted antibody class switching of B cells, which may be mediated by inducing Tfh2 cells, yet the study was not completely dependent on Tfh cells. The results provide evidence of the B cell response to an immune suppressive environment by evaluating IgG4 antibodies, and established a relationship between IgG4+ B cells and Tfh2 cells. Clarification of lymphocyte functions in the inflammatory microenvironment of tumors will be of potential therapeutic value.
前列腺癌是男性最常见的恶性肿瘤，容易发展为侵袭性肿瘤，这与原位慢性炎症肿瘤微环境密切相关。本研究旨在评估前列腺癌患者B细胞的免疫球蛋白G（IgG）亚类，并探讨它们与滤泡辅助性T（Tfh）亚群的相互作用。通过FACSAria分析或分选外周血中幼稚B细胞、记忆B细胞和成熟B细胞以及Tfh1、Tfh2和Tfh17细胞的百分比。采用酶联免疫吸附测定（ELISA）检测不同IgG亚类（IgG1、IgG2、IgG3和IgG4）的比例，运用逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹分析检测CXCR3和CCR6的表达水平。同时建立B细胞和Tfh细胞共培养体系，以评估各Tfh亚群对体外B细胞抗体亚类转换的影响。我们观察到前列腺癌患者中3种Tfh亚群和IgG4+B细胞的百分比高于健康对照，并证实Tfh2与IgG4+B细胞之间呈正相关。随后我们证实白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和前列腺素E2（PGE2）可有效促进B细胞的抗体类别转换，这可能是通过诱导Tfh2细胞介导的，但该研究并不完全依赖于Tfh细胞。这些结果通过评估IgG4抗体为B细胞对免疫抑制环境的反应提供了证据，并建立了IgG4+B细胞与Tfh2细胞之间的关系。阐明肿瘤炎症微环境中的淋巴细胞功能具有潜在的治疗价值。
