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

• Published in: Immunology letters Vol. 214; pp. 16 - 22
• Main Authors: Koushaeian, Ladan, Ghorbani, Farzaneh, Ahmadi, Majid, Eghbal-Fard, Shadi, Zamani, Majid, Danaii, Shahla, Yousefi, Bahman, Jadidi-Niaragh, Farhad, Hamdi, Kobra, Yousefi, Mehdi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2019
• Subjects: Adolescent; Adult; Autoantibody; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Embryo Implantation - immunology; Female; Humans; Imiquimod - pharmacology; Interleukin-10; Interleukin-10 - blood; Interleukin-10 - immunology; Oligodeoxyribonucleotides - pharmacology; Pregnancy; Pregnancy Complications - blood; Pregnancy Complications - immunology; Regulatory B cells; Repeated implantation failure; XBP1; Interleukin-10; Repeated implantation failure; Autoantibody; Regulatory B cells; RIF; IL-10; ET; IRF4; ODN; PD-L1; TLR; PCR; BLIMP1; ELISA
• ISSN: 0165-2478; 1879-0542; 1879-0542
• DOI: 10.1016/j.imlet.2019.08.002

•Decrease in IL-10- producing B cells and their related IL-10 in woman with RIF.•Negative association between the percentage of IL-10- producing B cells and level of serum autoantibodies in RIF patients.•lower levels of IL-10- producing B cells were found in patients with larger number of failed ET. 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.