Decrease in the proportion of CD24hiCD38hi B cells and impairment of their regulatory capacity in type 1 diabetes patients

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)-gamma, tumor necrosis factor (TNF)-alpha 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 center dot 6 +/- 3 center dot 5 versus 6 center dot 9 +/- 3 center dot 3%; P 0 center dot 05), produced less IL-10 (15 center dot 4 +/- 4 center dot 3 versus 29 center dot 0 +/- 4 center dot 5%; P 0 center dot 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-gamma(+) and CD4(+)TNF-alpha(+) T cells (r = -0 center dot 248 and r = -0 center dot 283, P = 0 center dot 008 and P = 0 center dot 017, respectively), positively correlating with the frequency of CD4(+)CD25(+)FoxP3(+) T cells (r = 0 center dot 247, P = 0 center dot 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.