Lee Hwa-Joung, Seo Goo-Young, Kim Hyun-A, Kim Pyeung-Hyeun
Department of Molecular Bioscience, School of Bioscience & Biotechnology, Kangwon National University, Chunchon 200-701, Republic of Korea.
Biochem Biophys Res Commun. 2008 Feb 8;366(2):574-8. doi: 10.1016/j.bbrc.2007.12.008. Epub 2007 Dec 10.
In this study, a potential role for activin A in mouse immunoglobulin (Ig) regulation was investigated. We observed that activin A increased IgA secretion in B lymphoma cells. In contrast, little effect was observed on IgM and IgG2b secretion. Activin A also significantly increased surface IgA expression and Ig germ-line alpha transcript (GLT(alpha)) levels. In parallel, activin A increased GLT(alpha) and post-switch transcripts alpha (PST(alpha)) expression in normal B cells, which was augmented by IL-5. An increase in IgA production by surface IgA negative B cells by activin A was apparent. Finally, the increase of IgA secretion by activin A was blocked by an activin receptor inhibitor (SB431542). The increase of GLT(alpha) by activin A was augmented by Smad3/4 overexpression and abolished by Smad3 dominant negative overexpression. These results suggest that activin A induces IgA isotype switching via Smad3/4-mediated germ line alpha transcription.
在本研究中，对激活素A在小鼠免疫球蛋白（Ig）调节中的潜在作用进行了研究。我们观察到激活素A增加了B淋巴瘤细胞中IgA的分泌。相比之下，对IgM和IgG2b分泌的影响很小。激活素A还显著增加了表面IgA的表达以及Ig胚系α转录本（GLT(α)）水平。同时，激活素A增加了正常B细胞中GLT(α)和转换后转录本α（PST(α)）的表达，白细胞介素-5可增强这种作用。激活素A使表面IgA阴性B细胞的IgA产生明显增加。最后，激活素受体抑制剂（SB431542）阻断了激活素A诱导的IgA分泌增加。激活素A诱导的GLT(α)增加在Smad3/4过表达时增强，而在Smad3显性负性过表达时被消除。这些结果表明，激活素A通过Smad3/4介导的胚系α转录诱导IgA同种型转换。
