Benzene induces spleen injury through the B cell receptor signaling pathway

Abstract

Benzene is a toxic environmental pollutant that disrupts the immune system in humans. Benzene exposure reduces the abundance of immune cells in multiple immune organs; however, the biological mechanisms underlying benzene-induced immunotoxicity has not been elucidated. In this study, benzene was used to develop mouse model for immune dysfunction. A significant decrease in IgG, IL-2 and IL-6 levels, an increase in oxidative stress and spleen injury were observed after benzene exposure in a dose-dependent manner. Quantitative proteomics revealed that benzene-induced immune dysfunction was associated with deregulation of the B cell receptor (BCR) signaling pathway. Benzene exposure suppressed the expression of CD22, BCL10 and NF-κb p65. Also, a significant decrease in proliferation and an increase in apoptosis of splenic lymphocytes were found after benzene exposure. Moreover, we found that benzene exposure increased mitochondrial reactive oxygen species (mito-ROS) and decreased adenosine triphosphate (ATP). Overall, we revealed the damaging effects of benzene on spleen-related immune function and the underlying biological mechanism, involving the disruption of BCR signaling pathway, NF-κB deactivation, and mitochondrial dysfunction.