Collins J T, Dunnick W A
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109-0620.
Int Immunol. 1993 Aug;5(8):885-91. doi: 10.1093/intimm/5.8.885.
The switch in expression by B cells from IgM to IgG, IgE, or IgA is accomplished by a DNA deletion. The deletion event is regulated, in that specific cytokines direct the B cell to switch to one, or sometimes two, of the six possible murine heavy chain genes. Prior to switch recombination, cytokine treatment also induces the transcription of the constant, switch, and upstream regions of the targeted heavy chain. Much evidence indicates that IFN-gamma directs switch recombination to the murine gamma 2a gene. By developing probes specific for the gamma 2a gene, we demonstrate that IFN-gamma increases germline transcription of this gene in both normal B cells and in the 18.81.A20 pre-B lymphoma. We have obtained cloned copies of three different germline gamma 2a transcripts, each with a different donor splice site. We have also located the 5' ends of these transcripts. The vast majority of the germline gamma 2a transcripts have a long first exon (> 700 bp), consistent with observations by Severinson and her colleagues.
B细胞从IgM到IgG、IgE或IgA的表达转换是通过DNA缺失实现的。这种缺失事件是受调控的，因为特定的细胞因子会引导B细胞转换到六个可能的小鼠重链基因中的一个，有时是两个。在转换重组之前，细胞因子处理还会诱导靶向重链的恒定区、转换区和上游区域的转录。大量证据表明，干扰素-γ会引导转换重组至小鼠γ2a基因。通过开发针对γ2a基因的特异性探针，我们证明干扰素-γ会增加该基因在正常B细胞和18.81.A20前B淋巴瘤中的种系转录。我们获得了三种不同种系γ2a转录本的克隆拷贝，每个转录本都有不同的供体剪接位点。我们还确定了这些转录本的5'末端。绝大多数种系γ2a转录本都有一个长的第一外显子（>700 bp），这与塞弗林森及其同事的观察结果一致。
