循环滤泡辅助 T 细胞功能异常导致骨肉瘤患者 B 细胞成熟和分化的不同表现。

Abnormal Function of Circulating Follicular Helper T Cells Leads to Different Manifestations of B Cell Maturation and Differentiation in Patients with Osteosarcoma.

机构信息

Department of Traumatic Orthopaedics, Dongying People's Hospital, Dongying, Shandong, China.

Department of Radiology, Dongying People's Hospital, Dongying, Shandong, China.

出版信息

J Healthc Eng. 2022 Apr 19;2022:3724033. doi: 10.1155/2022/3724033. eCollection 2022.

DOI:10.1155/2022/3724033

PMID:35494526

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9042599/

Abstract

OBJECTIVE

The objective of this study is to investigate the effect of dysfunctional circulating follicular helper T cells (Tfh) on B cell maturation and differentiation in patients with osteosarcoma (OS).

METHOD

Data from 30 OS patients who underwent diagnosis and treatment in our hospital, as well as those of 30 healthy subjects (HC), were collected at the same time. Flow cytometry was employed to identify proportions of CD4+CXCR5+Tfh cells and Tfh cell subtypes Tfh17, Tfh1, and Tfh2 in the patient's peripheral blood. CD40 L and IFN levels were detected after stimulating Tfh cells with an influenza antigen; the positive rates of CD27 and CD38 in B cells were detected before and after coculture with Tfh cells. qRT-PCR was carried out for Blimp-1 expression in B cells, and ELISA was employed to identify the levels of IgM, IgG, and IgA in B cells and IL-2, IL-10, and IL-4 in Tfh cells before and after coculture.

RESULTS

The percentage of CD4+CXCR5+Tfh cells in OS patients' peripheral blood increased significantly. The Tfh cell ratio increased along with the TNM stage, and the Tfh cell ratio in OS metastasis patients is greater than that in nonmetastatic patients. In addition, Tfh2 and Tfh17 cells increased drastically in OS patients, and no meaningful change was seen in Tfh1 cells. CD40 L levels of Tfh cells in OS patients were less than those of the HC group, and IFN was substantially increased. After coculturing the OS group's B cells with Tfh cells, the CD27+ and CD38+ cells of B cells were drastically greater, and Blimp-1 expression was also significantly increased. In addition, the levels of IL-21, IL-4, and IL-10 of Tfh cells in the OS group and the levels of IgA, IgG, and IgM in B cells were significantly reduced after coculture.

CONCLUSION

Dysfunctional Tfh in OS patients can severely inhibit B cell development, maturation, and differentiation.

摘要

目的

本研究旨在探讨功能失调的循环滤泡辅助 T 细胞（Tfh）对骨肉瘤（OS）患者 B 细胞成熟和分化的影响。

方法

同时收集我院 30 例 OS 患者和 30 例健康对照者（HC）的诊断和治疗数据。采用流式细胞术鉴定患者外周血中 CD4+CXCR5+Tfh 细胞及 Tfh 细胞亚群 Tfh17、Tfh1 和 Tfh2 的比例。用流感抗原刺激 Tfh 细胞后检测 CD40L 和 IFN 水平；Tfh 细胞与 B 细胞共培养前后检测 CD27 和 CD38 的阳性率。qRT-PCR 检测 B 细胞中 Blimp-1 的表达，ELISA 检测共培养前后 B 细胞中 IgM、IgG 和 IgA 及 Tfh 细胞中 IL-2、IL-10 和 IL-4 的水平。

结果

OS 患者外周血中 CD4+CXCR5+Tfh 细胞比例明显升高。Tfh 细胞比例随 TNM 分期升高而升高，OS 转移患者 Tfh 细胞比例大于非转移患者。此外，OS 患者 Tfh2 和 Tfh17 细胞明显增加，Tfh1 细胞无明显变化。OS 患者 Tfh 细胞的 CD40L 水平低于 HC 组，IFN 显著升高。OS 组 B 细胞与 Tfh 细胞共培养后，B 细胞的 CD27+和 CD38+细胞明显增多，Blimp-1 表达也明显增加。此外，OS 组 Tfh 细胞的 IL-21、IL-4 和 IL-10 水平以及 B 细胞的 IgA、IgG 和 IgM 水平在共培养后均显著降低。