Seo Goo-Young, Youn Jeehee, Kim Pyeung-Hyeun
Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea.
J Leukoc Biol. 2009 May;85(5):744-50. doi: 10.1189/jlb.0708450. Epub 2009 Jan 23.
It is well established that TGF-beta1 induces IgA and IgG2b class-switching recombination in murine B cells. In the present study, we assessed the activity of IL-21 along with TGF-beta1 in Ig synthesis by murine spleen B cells. IL-21 showed antiproliferative activity on LPS-activated splenic B cells, comparable with that of TGF-beta1. IL-21 alone had little effect on IgA secretion and decreased other isotypes. Likewise, IL-21 also did not alter the TGF-beta1-induced IgA synthesis and concurrently diminished the syntheses of IgM and IgG2a, which were repressed by TGF-beta1. Unexpectedly, IL-21 inhibited the TGF-beta1-induced IgG2b production. This IL-21 effect was examined using B cells from IL-21R knockout mice, where the IgA production profile was paralleled by that seen in wild-type B cells. However, the inhibitory effect of IL-21 on TGF-beta1-induced IgG2b synthesis was not seen in the IL-21R(-/-) mouse, suggesting that IL-21 causes TGF-beta1-stimulated B cells to decrease IgG2b synthesis. Expression patterns of Ig germ-line alpha(GL alpha)/GL gamma 2b transcripts under the influence of TGF-beta1 and IL-21 were paralleled by IgA/IgG2b secretion. This was also observed in the activities of GL(alpha) and GL(gamma 2b) promoters. These results indicate that IL-21 decreases IgG2b secretion mainly through inhibition of GL(gamma 2b) transcription and is ultimately associated with selective IgA secretion induced by TGF-beta1. Our results showed that IL-21 was expressed in greater magnitude in Peyer's patches (PP) than in spleen. These results suggest that IL-21 has an important effect on selective IgA(+) B cell commitment in PP.
众所周知，转化生长因子β1（TGF-β1）可诱导小鼠B细胞发生IgA和IgG2b类别转换重组。在本研究中，我们评估了白细胞介素21（IL-21）与TGF-β1共同作用对小鼠脾脏B细胞免疫球蛋白（Ig）合成的影响。IL-21对脂多糖（LPS）激活的脾脏B细胞具有抗增殖活性，与TGF-β1相当。单独的IL-21对IgA分泌影响不大，但可降低其他同种型。同样，IL-21也不改变TGF-β1诱导的IgA合成，同时减少了TGF-β1所抑制的IgM和IgG2a的合成。出乎意料的是，IL-21抑制了TGF-β1诱导的IgG2b产生。使用来自IL-21受体敲除小鼠的B细胞检测了这种IL-21效应，其IgA产生情况与野生型B细胞相似。然而，在IL-21R基因敲除（IL-21R(-/-)）小鼠中未观察到IL-21对TGF-β1诱导的IgG2b合成的抑制作用，这表明IL-21可使TGF-β1刺激的B细胞减少IgG2b合成。在TGF-β1和IL-21影响下，Ig胚系α（GLα）/GLγ2b转录本的表达模式与IgA/IgG2b分泌情况相似。在GLα和GLγ2b启动子活性方面也观察到了同样的情况。这些结果表明，IL-21主要通过抑制GLγ2b转录来减少IgG2b分泌，最终与TGF-β1诱导的选择性IgA分泌相关。我们的结果显示，IL-21在派尔集合淋巴结（PP）中的表达量高于脾脏。这些结果表明，IL-21对PP中选择性IgA(+) B细胞的定向分化具有重要作用。
