Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
J Immunol. 2011 Jan 1;186(1):350-8. doi: 10.4049/jimmunol.1003108. Epub 2010 Dec 3.
Germline transcription precedes class switch recombination (CSR). The promoter regions and I exons of these germline transcripts include binding sites for activation- and cytokine-induced transcription factors, and the promoter regions/I exons are essential for CSR. Therefore, it is a strong hypothesis that the promoter/I exons regions are responsible for much of cytokine-regulated, gene-specific CSR. We tested this hypothesis by swapping the germline promoter and I exons for the murine γ1 and γ2a H chain genes in a transgene of the entire H chain C-region locus. We found that the promoter/I exon for γ1 germline transcripts can direct robust IL-4-induced recombination to the γ2a gene. In contrast, the promoter/I exon for the γ2a germline transcripts works poorly in the context of the γ1 H chain gene, resulting in expression of γ1 H chains that is <1% the wild-type level. Nevertheless, the small amount of recombination to the chimeric γ1 gene is induced by IFN-γ. These results suggest that cytokine regulation of CSR, but not the magnitude of CSR, is regulated by the promoter/I exons.
种系转录先于类别转换重组（CSR）。这些种系转录本的启动子区域和 I 外显子包含激活和细胞因子诱导转录因子的结合位点，并且启动子区域/I 外显子对于 CSR 是必不可少的。因此，一个强有力的假设是，启动子/I 外显子区域负责大部分细胞因子调节的、基因特异性的 CSR。我们通过在整个 H 链 C 区基因座的转基因中交换 γ1 和 γ2a H 链的种系启动子和 I 外显子来检验这一假设。我们发现，γ1 种系转录本的启动子/I 外显子可以指导强大的 IL-4 诱导重组到 γ2a 基因。相比之下，γ2a 种系转录本的启动子/I 外显子在 γ1 H 链基因的背景下效果不佳，导致 γ1 H 链的表达水平<野生型的 1%。然而，小量的重组到嵌合的 γ1 基因是由 IFN-γ诱导的。这些结果表明，CSR 的细胞因子调节，而不是 CSR 的幅度，是由启动子/I 外显子调节的。
