Bidirectional effects of IL-10+ regulatory B cells in Ldlr−/− mice

Abstract Background and aims Limiting the pro-inflammatory immune response is critical for the treatment of atherosclerosis. Regulatory B cells (Bregs) can modulate the immune response through interleukin-10 (IL-10). Current data regarding Bregs and atherosclerosis is scarce and conflicting. Methods In this study, we investigated the frequency of IL-10 + B cells during the development of atherosclerosis in low-density lipoprotein receptor-deficient ( Ldlr −/− ) mice and studied the effect of adoptive transfer of IL-10 + B cells on atherosclerosis. Results We found a very strong inverse correlation between atherosclerosis severity and the frequency of IL-10 + B cells. This effect was cholesterol-independent and observed in spleen, draining lymph nodes and peritoneal cavity. To directly assess the effects of IL-10 + B cells on atherosclerosis, we expanded IL-10 + B cells ex vivo with anti-CD40 and selected pure and viable IL-10-secreting B cells and IL-10 - B cells and adoptively transferred them to Ldlr −/− mice, respectively. While IL-10 - B cells were strongly atherogenic compared to control-treated mice, IL-10 + B cells did not affect lesion size. Adoptive transfer of IL-10 + B cells strongly reduced circulating leukocyte numbers and inflammatory monocytes. In addition, they decreased CD4 + T cell activation and increased IL-10 + CD4 + T cell numbers. Interestingly, both IL-10 + and IL-10 - B cells exacerbated serum cholesterol levels and resulted in fatty livers, which potentially masked the beneficial effects of IL-10 + B cells on atherosclerosis. Conclusions These findings underscore the strong immune-regulating function of IL-10 + B cells and provide additional incentives to explore effective strategies that expand IL-10 + B cells in atherosclerosis.