Decrease in the proportion of CD24 hi CD38 hi B cells and impairment of their regulatory capacity in type 1 diabetes patients

Summary B10 cells restore immune balance by producing interleukin (IL)‐10. Impaired B10 cell responses are related to numerous autoimmune diseases. However, the function of B10 cells in type 1 diabetes (T1D) patients is controversial. We hypothesized that there are numerical and functional defects of B10 cells in T1D. Sixty‐two patients with T1D and 74 healthy volunteers were included in our study. We showed that B10 cells in human peripheral blood belong to a CD24 hi CD38 hi B cell subpopulation. CD24 hi CD38 hi B cells from healthy individuals possessed regulatory capacity, suppressed interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α and IL‐17A production and promoted IL‐4 production and forkhead box protein 3 (FoxP3) expression in CD4 + T cells through an IL‐10‐dependent mechanism. Compared to healthy controls, B10 cell percentages in T1D were significantly lower (5·6 ± 3·5 versus 6·9 ± 3·3%; P <  0·05), produced less IL‐10 (15·4 ± 4·3 versus 29·0 ± 4·5%; P <  0·001) and lacked regulatory capacity. In addition, Pearson’s correlation analysis showed that the frequency of circulating B10 cells was negatively correlated with the frequency of CD4 + IFN‐γ + and CD4 + TNF‐α + T cells ( r  = −0·248 and r  = −0·283, P  = 0·008 and P  = 0·017, respectively), positively correlating with the frequency of CD4 + CD25 + FoxP3 + T cells ( r  = 0·247, P  = 0·001). These data offer direct proof that there is a deficiency of circulating CD24 hi CD38 hi B cells in peripheral blood of patients with T1D, which participate in the T1D immune imbalance involved in the development of T1D.