One of the most profound enigmas in B cell biology is how activation-induced deaminase (AID) is targeted to a very small region of DNA in the immunoglobulin loci. Two specific regions are singled out: the variable region of 2 kb that contains rearranged genes on the heavy, κ light, and λ light chain loci, and the switch region of ∼4 kb that contains an extensive stretch of G:C rich DNA on the heavy chain locus. Transcription is required for AID recruitment; however, many genes are also highly transcribed and do not undergo the catastrophic mutagenesis that occurs in variable and switch regions. The DNA sequences of these regions cause RNA polymerase II to accumulate for an extended distance of 2–4 kb. The stalled polymerases then recruit the transcription cofactor Spt5, and AID, which deaminates cytosines to uracils in exposed transcription bubbles. Thus, the immunoglobulin loci are unique in that a favorable combination of DNA sequences and 3′ transcription enhancers make them the perfect storm for AID-induced somatic hypermutation.

中文翻译：

---

什么针对免疫球蛋白基因座进行体细胞超突变？

B细胞生物学中最深刻的谜团之一是如何将激活诱导的脱氨酶（AID）靶向免疫球蛋白基因座中很小的DNA区域。挑出了两个特定区域：2 kb的可变区，在重链，κ轻链和λ上包含重排基因轻链基因座，以及〜4 kb的开关区域，在重链基因座上含有大量的富含G：C的DNA。AID招聘需要转录；但是，许多基因也被高度转录，并且不会发生在可变和转换区域发生的灾难性诱变。这些区域的DNA序列会导致RNA聚合酶II积累2–4 kb的延长距离。停滞的聚合酶随后募集转录辅因子Spt5和AID，后者将胞嘧啶脱氨为暴露的转录气泡中的尿嘧啶。因此，免疫球蛋白基因座的独特之处在于，DNA序列和3'转录增强子的良好组合使其成为AID诱导的体细胞超突变的理想之选。