Expression Level of Autoimmune Regulator In B Cells Correlates With Residual Islet β Cell Function In Type 1 Diabetes Mellitus

Abstract

Background Autoimmune modulators (Aire) mediate immune tolerance by inducing expression of tissue-restricted antigen (TRA) in thymic medullary epithelial cells. However, the function of Aire in peripheral B cells remains unknown. We aimed to investigate whether Aire is expressed in human peripheral B cells and how its expression is regulated. Methods Human thymus tissues were collected and firstly, islet-specific autoantibodies and insulinogen c-peptide were determined by luciferase immunoprecipitation (LIPS). Secondly, Aire expression in peripheral blood lymphocytes was identified by flow cytometry, Western Blot and immunofluorescent staining. Then, immunofluorescent staining was performed on cells cultured in vitro and surgically resected tissues. Meanwhile, Aire promoter methylation. Finally, insulinogen expression was quantified by reverse transcription qPCR and IF staining. Data were compared by Mann-Whitney U test between groups. Results Aire was expressed in CD19⁺ B cells but not in CD3⁺ cells, and the expression of Aire in B cells was much lower than that in thymus. Induction of Aire expression under BCR activation in B cells. The level of Aire expression in peripheral B cells of patients with T1D and healthy subjects showed no difference in Aire expression level between the two groups. Conclusions Aire expression in peripheral B cells may play a role in peripheral immune tolerance and protection of islet β-cell function in T1D patients.