The characteristic activity of regulatory B cells during the occurrence and development of insulin resistance.

Abstract

Purpose: To investigate the aberrant distribution and clinical relevance of regulatory B cells (Bregs) subsets in the peripheral blood of individuals with different levels of insulin resistance (IR).

Methods: A cohort of 124 subjects were divided into five groups according to their insulin resistance index (HOMA-IR) and diabetes diagnosis. The groups comprised Group 1 (IR^- with good glycemic control) and Group 2 (IR^- with poor glycemic control) at HOMA-IR < 3, Group 3 (IR⁺ without T2DM) and Group 4 (IR⁺ with T2DM), at 3 ≤ HOMA-IR < 6, and Group 5 (IR⁺⁺ with T2DM) at HOMA-IR ≥ 6. Peripheral blood samples were collected from each group, the percentages of CD19⁺CD24⁺CD27⁺ and CD19⁺CD24⁺CD38⁺ Bregs and the levels of IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFN-γ were detected by flow cytometry and flow microsphere matrix method. Additionally, the cytokines levels were validated through ELISA. The activation of Bregs and the production of IL-10 among different groups were analyzed. Spearman correlation analysis was used to analyze the correlation between Bregs activation rate and IR degree.

Results: The results showed that the levels of CD19⁺CD24⁺CD27⁺ and CD19⁺CD24⁺CD38⁺ cells were increased whether in IR⁺ without or with type 2 diabetes mellitus (T2DM) groups compared to the IR^- groups, with the most significant increase observed in Group 5. Moreover, the plasma levels of IL-6, IL-10, IL-17, TNF-α and IFN-γ in the IR⁺ group were higher than those in the IR^- group. The expression and activation level of Bregs were positively correlated with the severity of IR in T2DM.

Conclusion: These results suggest that the increase level of Bregs is closely related to the severity of IR, highlighting the potential significance of Bregs in the clinical progression of T2DM and its associated insulin resistance.