The role of IL-10-producing B cells in repeated implantation failure patients with cellular immune abnormalities

Abstract

There are a few data of the role of B cells in RIF pathogenesis. Accordingly, the objective of the current study was to determine the role of IL-10-producing B cells in RIF. Twenty-three RIF women with cellular immune abnormalities and 25 normal controls were enrolled in this experiment. Isolated naïve B cells from peripheral blood of the subjects were cultured in vitro, divided into two parts and activated by CpG ODN and imiquimod as TLR agonists. Afterwards, the number of CD19⁺ IL-10⁺ B cells was evaluated by flow cytometry and their related IL-10 cytokine level was assessed by ELISA. The mRNA expression levels of related genes in just CPG stimulated B cell population were also analyzed using real-time PCR. RIF patients exhibited a decreased level of the cells (P = 0.014, P = 0.023, respectively) and IL-10 cytokine (P = 0.009, P = 0.045, respectively) in both CPG and imiquimod stimulated B cell groups. IL-10 serum level was also lower in these patients (P = 0.0014). Additionally, we found a negative relationship between the frequency of these cells with the number of failed ET and total IgG titers in RIF patients. The mRNA levels of IL-10-producing B cells related genes (IL-10 and PD-L1) was also significantly lower in RIF women, whereas the expression of plasma cells-associated transcriptional factors (BLIMP1, IRF4, and XBP1) was higher. Summing up the obtained results, we concluded that peripheral blood IL-10-producing B cells down-regulation might result in RIF pathogenesis. It is further suggested that these cells can suppress autoantibody generation and contribute to a successful implantation.

Keywords: Autoantibody; Interleukin-10; Regulatory B cells; Repeated implantation failure.