The Effect of miR-138 on the Function of Follicular Helper T Cells and the Differentiation of B Cells in Osteosarcoma

OBJECTIVE: To explore the effect of miR-138 on the function of follicular helper T (Tfh) cells and the differentiation of B cells in osteosarcoma. METHODS: Clinically collect peripheral blood from osteosarcoma (OS) patients and healthy volunteers (HC), as well as OS tumor tissues (OS tumor) and adjacent tissues with normal histology (normal group). The CD4(+)CXCR5(+)Tfh cells of OS patients were screened and isolated by flow cytometry, and the expression of Tfh cell membrane surface antigens PD-1 and CTLA-4 was detected. In addition, qRT-PCR was used to detect the expression of miR-138 in tissues and Tfh cells, and the correlation relationship between miR-138 and PD-1 and CTLA-4 was analyzed. After interference or overexpression of miR-138 in Tfh cells, coculture with untreated B cells was done, and the levels of IL-10, IL-12, IL-21, and INF-γ in Tfh cell culture medium and the levels of IgM, IgG, and IgA in B cell culture medium after coculture were measured by ELISA. Flow cytometry was used to detect the expression of B cell membrane surface antigens CD27 and CD38 after coculture. RESULTS: The rate of PD-1- and CTLA-4 positive cells in the peripheral blood and tissues of the OS group was significantly increased, the expression of miR-138 was significantly reduced, and the expression of miR-138 was negatively correlated with the expression of PD-1 and CTLA-4. In addition, upregulation of miR-138 can lead to a significant increase in the level of IL-10 in the supernatant of Tfh cells and a significant decrease in the levels of IL-12, IL-21, and INF-γ, which in turn leads to increased levels of IgM, IgG, and IgA released by B cells. At the same time, it significantly increases the rate of CD27- and CD38-positive cells and promotes the maturation of B cells. Downregulating miR-138 has the opposite effect. CONCLUSION: Downregulating the expression of miR-138 in osteosarcoma can improve the dysfunction of CD4(+)CXCR5(+)Tfh cells and promote the differentiation of B cells.