Atherosclerosis is a major trigger of myocardial infarction and constitutes the leading cause of cardiovascular mortality. Atherosclerosis is a chronic inflammatory disease involving the infiltration of immune cells, such as monocytes/ macrophages, neutrophils, T and B ells, into the inner layer of vessel walls. B cells functions in the process of atherogenesis have been investigated but several aspects remain to be clarified. In the present study, we show that follicular regulatory helper T cells (Tfr) controls regulatory B cell (Breg) population in ApoE-/- mice models under high-cholesterol diet (HCD). Feeding mice with HCD resulted in upregulation of Tfr cell and Breg cell populations leading to suppression of proatherogenic Tfh response. Tfh cells modulation is correlated with the development of atherosclerotic plaque size in thoraco-abdominal aortas and aortic root plaques suggesting that Tfr are atheroprotective. Marginal zone B cell (MZB cell) and follicular B cell (FOB cell) population are increased and decreased respectively by HCD but seems to be not regulated by Tfr. Using adoptive transfer experiments, Tfr cells transferred into HCD mice induce a decrease of Tfh cell population and atherosclerotic plaque size while Breg cells population is significantly increased. Our results demonstrate that Tfr and Tfh modulate anti- and pro-atherosclerotic immune process in ApoE-/- mice model. Tfr cells being able to regulate Breg cell population. We further shown that, although Tfr are potent to prevent atherogenesis, they are unable to reduce established atherosclerosis plaques. Consequently, ex vivo expansion of Tfr cell population could thus be use for cellular therapy as primary but not as secondary treatment of atherosclerosis patients.