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

SM Richards, EA Clark - European journal of immunology, 2009 - Wiley Online Library
SM Richards, EA Clark
European journal of immunology, 2009Wiley Online Library
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 gp91phox subunit of the NADPH oxidase complex
are unable to generate ROS after BCR ligation. However, after BCR stimulation, more
gp91phox KO B cells enter the G1 stage of the cell cycle and proliferate than WT B cells …
Abstract
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 gp91phox subunit of the NADPH oxidase complex are unable to generate ROS after BCR ligation. However, after BCR stimulation, more gp91phox 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 p27Kip1 levels in gp91phox KO B cells. Gp91phox 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.
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