Decrease in Proportion of CD24hiCD38hi Beta Cells and Impairment of Their Regulatory Capacity in Type 1 Diabetes Patients

Abstract

Several studies have shown a subset of B cells play an important role in regulating the autoimmune response via the production of interleukin-10 known as B10 cells. However, the role of B10 cells in type 1 diabetes (T1D) and their relevance to the maintenance of peripheral tolerance in humans remains elusive. The aim of this study was to investigate the role of B10 cells in the pathogenesis of T1D. Peripheral mononuclear blood cells of 62 patients with T1D and 74 healthy volunteers were included. We showed that B10 cells in human peripheral blood belonged to a CD24hiCD38hi B cell subpopulation. Additionally, CD24hiCD38hi B cells from healthy individuals possessed regulatory capacity, inhibited IFN-γ, TNF-α and IL-17 production and promoted IL-4 production and Foxp3 expression of CD4+ T cells via an IL-10-dependent pathway. Compared with healthy controls, the proportion of B10 cells in patients with T1D was significantly lower (5.6±3.5% vs. 6.9±3.3%; P <0.05), produced less IL-10 (15.4±4.3% vs. 29.0±4.5%; P <0.001), and lacked the regulatory capacity. Pearson correlation analysis showed that the frequency of circulating B10 cells were negatively correlated with the frequency of CD4+IFN-γ+ and CD4+TNF-α+ T cells(r=-0.3and r=-0.360,P=0.037 and P=0.021, respectively), and positively correlated with the frequency of CD4+ CD25+ Foxp3+ T cells(r=0.018,P=0.001). There was also a negatively correlation between the frequency of circulating B10 cells and HbA1c(r=-0.339,P=0.010). These data provide direct evidence that there is a deficiency of circulating CD24hiCD38hi B cells in peripheral blood of patients with T1D, which might take part in the T1D immune imbalance, involved in the development of T1D. Disclosure Y. Wang: None. X. Wang: None. Y. Qin: None. M. Zhang: None.