title: iNOS potentiates mouse Ig isotype switching through AID expression.
abstract: 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.
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Mi-Ra
authors.initials: MR
authors.lastname: Lee
authors.forename: Goo-Young
authors.initials: GY
authors.lastname: Seo
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Pyeung-Hyeun
authors.initials: PH
authors.lastname: Kim
mesh_terms: D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics*; D005786:Gene Expression Regulation; D007070:Immunoglobulin A / Q000235:genetics*; D017578:Immunoglobulin Class Switching; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000502:physiology*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D007070:Immunoglobulin A; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase