Essential roles of the κ light chain intronic enhancer and 3′ enhancer in κ rearrangement and demethylation

The kappa intronic (MiE(kappa)) and 3' (3'E-kappa) enhancers are both quantitatively important to, but not essential for, immunoglobulin kappa rearrangement. To determine the functional redundancy between these two enhancers, B cells derived from mutant embryonic stem cells-in which both MiE(kappa) and 3'E-kappa were deleted on both kappa alleles-were analyzed for kappa rearrangement. Our findings indicate that these double-mutant B cells have essentially no kappa rearrangement but do rearrange and express lambda. Therefore, these two kappa enhancers share essential roles in activatingV(kappa)J(kappa) rearrangement. Our findings also indicate that the two kappa enhancers play overlapping and distinct roles in the demethylation of kappa in B cells.