کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1930541 | 1050517 | 2011 | 6 صفحه PDF | دانلود رایگان |
The IgA antibody plays an important role in protecting mucosal surfaces against pathogens. It has recently been shown that nitric oxide (NO) plays a critical role in mouse IgA synthesis. In the present study, we further characterized inducible-nitric oxide synthase-deficient (iNOS−/−) mice in the context of Ig expression. The amount of IgA in fecal pellets was substantially diminished in iNOS−/− mice and was paralleled by a decrease in IgA production by Peyer’s patch cells. Interestingly, the amount of all IgG subisotypes, as well as IgA, was substantially diminished in sera and in cultured spleen B cells from iNOS−/− mice. Moreover, the synthesis of TGF-β1-inducible IgA and IgG2b in iNOS−/− mice was also lower than that in WT mice. However, levels of Ig germ-line transcripts, and expression of TGF-β receptor type II (TβRII) and BAFF/APRIL, were comparable between iNOS−/− and WT mice. Expression of activation-induced cytidine deaminase (AID) was diminished in iNOS−/− B cells, but restored by a NO donor, SNAP. These results indicate that iNOS regulates Ig isotype switching events at the level of AID gene expression.
► In this study, we found that Ig class switch recombination (CSR) was significantly suppressed in iNOS−/− mice.
► This was paralleled by the decreased expression levels of AID, the single most critical enzyme in the CSR.
► Our results suggest that nitric oxide synthesized by iNOS mediates Ig CSR through the induction of AID.
Journal: Biochemical and Biophysical Research Communications - Volume 410, Issue 3, 8 July 2011, Pages 602–607