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- W2266895379 abstract "Generating a protective humoral immune response requires proper B cell activation. Ligation of the BCR increases the level of reactive oxygen intermediates (ROI). While they have been implicated in oxidative stress, recent studies suggest ROI act as secondary messengers facilitating normal cellular function. Our focus is on the mechanisms by which ROI control B cell function. Following BCR ligation in vitro, the levels of the first oxidation product of cysteine, sulfenic acid, increased in the proteome. Using 5,5-dimethyl-1,3-cyclohexanedione (dimedone), a compound that covalently reacts with sulfenic acid to prevent further oxidation or reduction, we determined reversible cysteine sulfenic acid formation is critical for sustained tyrosine phosphorylation, calcium flux, and proliferation of B cells. To address the role of ROI in vivo, lymphocytic choriomeningitis virus (LCMV) infected mice were treated with Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), a superoxide dismutase mimetic, from days 0-8 postinfection. On day 38, LCMV specific IgG antibody secreting cells (ASC) were 5-fold lower in the bone marrow. In contrast, the number of LCMV specific memory B cells was unaffected. The ASC decrease was not detected when mice were only treated from days 0-4 or 4-8 postinfection or during secondary viral infection. These data demonstrate ROI and reversible cysteine sulfenic acid formation are critical to B cell function and differentiation." @default.
- W2266895379 created "2016-06-24" @default.
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- W2266895379 date "2015-10-28" @default.
- W2266895379 modified "2023-10-18" @default.
- W2266895379 title "Ranjit Chandra: how reputation bamboozled the scientific community" @default.
- W2266895379 doi "https://doi.org/10.1136/bmj.h5683" @default.
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