The roles of E2A and Id2 in class switch recombination

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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).