BCR-induced superoxide negatively regulates B-cell proliferation and T-cell-independent type 2 Ab responses.

Superoxide and its derivatives have been implicated as secondary messenger molecules that influence signaling cascades in non-phagocytes. B lymphocytes produce superoxide after BCR ligation. We found that these ROS regulate B-cell signaling and entry into the cell cycle. B cells from mice deficient in the gp91(phox) subunit of the NADPH oxidase complex are unable to generate ROS after BCR ligation. However, after BCR stimulation, more gp91(phox) KO B cells enter the G1 stage of the cell cycle and proliferate than WT B cells. BCR ligation leads to a more rapid decrease in p27(Kip1) levels in gp91(phox) KO B cells. Gp91(phox) KO mice display enhanced T-cell-independent type 2, but normal T-dependent Ab responses. ROS-dependent regulation of BCR-induced proliferation may help modulate the size of the humoral response to T-cell-independent type 2 Ag immunization.