iNOS potentiates mouse Ig isotype switching through AID expression
iNOS potentiates mouse Ig isotype switching through AID expression
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DOI：
10.1016/j.bbrc.2011.06.035
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发表时间：
2011-07-08
影响因子：
3.1
通讯作者：
Kim, Pyeung-Hyeun
中科院分区：
文献类型：
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作者：
Lee, Mi-Ra;Seo, Goo-Young;Kim, Pyeung-Hyeun
伊加抗体在保护粘膜表面免受病原体侵害中起重要作用。最近的研究表明，一氧化氮（NO）在小鼠伊加合成中起着关键作用。在本研究中，我们进一步的特点诱导型一氧化氮合酶缺陷（iNOS（-/-））小鼠的背景下，IG表达。在iNOS（-/-）小鼠中，粪粒中伊加的量显著减少，并且通过派伊尔斑细胞的伊加产生减少而减少。有趣的是，所有IgG亚同种型以及伊加的量在血清和培养的iNOS（-/-）小鼠脾B细胞中显著减少。此外，iNOS（-/-）小鼠中TGF-β 1诱导的伊加和IgG 2b的合成也低于WT小鼠。然而，IG生殖系转录物的水平以及TGF-β受体II型（T β RII）和BAFF/APRIL的表达在iNOS（-/-）和WT小鼠之间是相当的。iNOS（-/-）B细胞中激活诱导的胞苷脱氨酶（AID）的表达减少，但通过NO供体SNAP恢复。这些结果表明iNOS在AID基因表达水平上调节IG同种型转换事件。(C)2011 Elsevier Inc. All rights reserved.
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-beta 1 -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-beta receptor type II (T beta RII) 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. (C) 2011 Elsevier Inc. All rights reserved.