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.
Richards
Sabrina M
SM
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Clark
Edward A
EA
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D005434:Flow Cytometry; D016193:G1 Phase; D007074:Immunoglobulin G / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D011947:Receptors, Antigen, B-Cell; D013481:Superoxides; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D002118:Calcium