Reactive oxygen species play roles on B cell surface receptor CD40-mediated proximal and distal signaling events: effects of an antioxidant, N-acetyl-L-cysteine treatment.

Reactive oxygen species (ROS) have been indicated as important signal mediators for many cell surface receptors. We previously demonstrated that ROS are generated by cross-linking surface receptor CD40 and consequently induce c-Jun N-terminal kinase activation and interleukin-6 secretion in murine B cells. In this study, we investigated further the involvement of ROS in CD40-mediated signaling events in B cells. CD40-mediated proximal events, which include protein serine phosphorylation, protein translocation between membranes and cytosol, as well as receptor complex formation, were inhibited after the pre-incubation of cells with an antioxidant N-acetyl-L-cysteine (NAC). Additionally, B cell responses after long-term ligation of CD40, such as protein expression, nuclear transcription factor kappaB (NFkappaB) activation, and cell proliferation, were also affected when cells were treated with NAC. These data suggest that CD40-induced ROS play critical roles in CD40-mediated B cell regulation.