B lymphocytes have been implicated in the development of insulin resistance, atherosclerosis and certain types of hypertension. In contrast to these studies, which were performed under pathological conditions, the present study provides evidence for the protective effect of B lymphocytes in maintaining vascular homeostasis under physiological conditions. In young mice not exposed to any known risk factors, the lack of B cells led to massive endothelial dysfunction. The vascular dysfunction in B cell-deficient mice was associated with an increased number of neutrophils in the circulating blood. Neutrophil depletion in B cell-deficient mice resulted in the complete normalization of vascular function, indicating a causal role of neutrophilia. Moreover, vascular function in B cell-deficient mice could be restored by adoptive transfer of naive B-1 cells isolated from wild-type mice. Interestingly, B-1 cell transfer also reduced the number of neutrophils in the recipient mice, further supporting the involvement of neutrophils in the vascular pathology caused by B cell-deficiency. In conclusion, we report in the present study the hitherto undescribed role of B lymphocytes in regulating vascular function. B cell dysregulation may represent a crucial mechanism in vascular pathology.