The downstream transcriptional enhancer, ed, positively regulates mouse IgK gene expression and somatic hypermutation

The mouse IgK locus has three known transcriptional enhancers: the matrix association region/intronic enhancer, the 3′ enhancer (E3′), and the further downstream enhancer (Ed). Previous studies have shown that both matrix association region/intronic and E3′ enhancers are required for maximal gene rearrangement of the locus, and that E3′ is also required for maximal expression and somatic hypermutation (SHM). To functionally elucidate Ed in vivo, we generated knockout mice with a targeted germline deletion of Ed. Ed deleted homozygous mice (Ed^-/-) have moderately reduced numbers of IgK expressing B cells and correspondingly increased numbers of Igλ expressing B cells in spleen. Ed^-/-mice also have decreased Igκ mRNA expression in resting and T cell-dependent activated splenic B cells and reduced Igκ chains in sera. However, our analysis indicates that Igκ gene rearrangement is normal in Ed^-/- mice. In addition, our results show that Ed^-/- mice exhibit reduced SHM in the Igκ gene J-C intronic region in germinal center B cells from Peyer's patches. We conclude that Ed positively regulates Igκ gene expression and SHM, but not gene rearrangement.