Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto University, Sakyo-ku, Kyoto, Japan.
J Immunol. 2010 Mar 15;184(6):2785-92. doi: 10.4049/jimmunol.0901823. Epub 2010 Feb 8.
IgA is a specific isotype required for mucosal immunity and is the most abundant Ab produced in vivo. Recently, several inductive signals for IgA class switch recombination have been identified; however, the molecular details of the action of these signals and the specific factors acting in B cells remain elusive. In this study, we show that combination of retinoic acid (RA) and TGF-beta1 with other factors induced a much higher frequency of IgA-switched cells than reported previously. In addition, IgA production is severely impaired in Runx2-Runx3 double-deficient mice. In Runx2-Runx3-deficient B cells, both RA- and TGF-beta1-dependent inductions of alpha germline transcription are completely blocked. These data suggest that Runx proteins play an essential role in IgA class switching acting downstream of RA and TGF-beta1 signaling.
IgA 是黏膜免疫所必需的特定同种型，也是体内产生最多的 Ab。最近，已经鉴定出几种 IgA 类别转换重组的诱导信号；然而，这些信号的作用的分子细节以及在 B 细胞中起作用的特定因子仍然难以捉摸。在这项研究中，我们表明，维甲酸 (RA) 和 TGF-β1 与其他因子的组合诱导的 IgA 转换细胞的频率比之前报道的要高得多。此外，Runx2-Runx3 双缺陷小鼠的 IgA 产生严重受损。在 Runx2-Runx3 缺陷 B 细胞中，RA 和 TGF-β1 依赖性α 种系转录的诱导完全被阻断。这些数据表明，Runx 蛋白在 RA 和 TGF-β1 信号下游的 IgA 类别转换中发挥重要作用。
