Tim‐1 + B cells suppress T cell interferon‐gamma production and promote Foxp3 expression, but have impaired regulatory function in coronary artery disease

Atherosclerosis and its associated coronary artery disease ( CAD ) represent another chronic low‐grade inflammatory disorder. Regulatory B cells (Bregs) possess essential functions in maintaining peripheral tolerance and inhibiting pathogenic inflammation through IL ‐10. Here, we investigated one subset of Bregs, Tim‐1 + B cell, and its role in atherosclerosis and CAD patients. In healthy individuals, IL ‐10‐producing B cells were predominantly found in the Tim‐1 + B cells. Upon stimulation of the B cell receptor ( BCR ) and Toll‐like receptor 9 ( TLR ‐9) by anti‐ BCR antibodies and CpG, respectively, the Tim‐1 + B cells could further upregulate IL ‐10 expression. In contrast, the Tim‐1 + B cells were present at normal frequency in CAD patients, but showed impaired capacity to upregulate IL ‐10 with or without BCR + CpG stimulation. The stimulated Tim‐1 + B cells from healthy individuals also suppressed expression of interferon gamma ( IFN ‐γ), an atherogenic cytokine in T cells, in an IL ‐10‐dependent fashion, and strongly promoted the expression of Foxp3 in naive CD 4 + CD 45 RO − T cells. In contrast, the Tim‐1 + B cells from CAD patients were unable to suppress IFN ‐γ secretion, and only minimally increased the expression of Foxp3 in naive CD 4 + CD 45 RO − T cells. Despite this, the frequency of Tim‐1 + B cells in the atherosclerotic lesions from CAD patients was inversely correlated with the frequency of IFN ‐γ‐expressing T cells. Together, these results demonstrated that CAD patients presented an inflammatory disorder in regulatory B cells, which could be used as a therapeutic target.