The roles of E2A and Id2 in class switch recombination

1.免疫球蛋白E（IgE）在变态反应性疾病的发病机制中起着中心作用，但其血清水平保持在正常人中比其他免疫球蛋白类低得多。在缺乏Id 2的B细胞中，E2 A的活性高度增强，增强ε种系转录，从而增强类转换重组（CSR）至IgE。相反，在野生型B细胞中，Id 2由TGF-β1诱导并抑制IgE CSR。这种抑制在Id 2缺陷型B细胞中不发生。我们的研究结果为Id 2在IgE CSR中的抑制和选择性作用提供了证据，特别是在对TGF-β1的反应中。表明Id 2是一种保护分子。2.Pax5活性在活化的B细胞中增强，并且对于类别转换重组（CSR）是必需的。我们发现，Id 2抑制CSR通过抑制激活诱导的胞苷脱氨酶（AID），这已被证明是必不可少的CSR的基因表达。此外，一个假定的调控区的AID含有E2 A和Pax 5结合位点，后者的网站是必不可少的AID基因表达。此外，Pax 5的DNA结合活性在Id 2过表达的B细胞中降低，而在Id 2 ^<-/-> B细胞中增强。在原代B细胞中，AID基因座的Pax 5占据而非E2 A占据的动力学与AID表达相同。最后，Pax 5的强制表达在pro-B细胞系中诱导AID转录。我们的研究结果表明E2 A、Pax 5和Id 2活性之间的平衡在AID基因表达中起着关键作用，Id 2作为负调节因子，可以防止过度免疫反应所带来的潜在有害影响：其特殊作用之一是维持低血清免疫球蛋白E（IgE）浓度。

1.Immunoglobulin E (IgE) plays a central,role in the pathogenesis of allergic disorders but its serum level is kept much lower than other immunoglobulin classes in normal. In B cells lacking Id2, the highly augmented activity of E2A enhances ε germline transcription, and thus class switch recombination (CSR) to IgE. In wild-type B cells, in contrast, Id2 is induced by TGF-β1 and suppresses IgE CSR. This suppression does not occur in Id2 deficient B cells. Our results provide evidence for the inhibitory and selective role of Id2 in IgE CSR, especially in response to TGF-β1. indicating Id2 is a safeguard molecule.2.Pax5 activity is enhanced in activated B cells and is essential for class switch recombination (CSR). We show that Id2 suppresses CSR by repressing the gene expression of activation-induced cytidine deaminase (AID), which has been shown to be indispensable for CSR. Furthermore, a putative regulatory region of AID contains E2A-and Pax5-binding sites and the latter site is indispensable for AID gene expression. Moreover, the DNA binding activity of Pax5 is decreased in Id2-overexpressing B cells, and enhanced in Id2^<-/-> B cells. The kinetics of Pax5-occupancy, but not E2A, to AID locus is the same as AID expression in primary B cells. Finally, enforced-expression of Pax5 induces AID transcription in pro-B cell lines. Our results provide evidence that the balance between E2A, Pax5 and Id2 activities has a key role in AID gene expression.Thus, Id2 acts as a negative regulator to prevent potentially harmful effects brought about by excessive immunological reactions: one of its special roles is to maintain low serum concentrations of immunoglobulin E (IgE).