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

The κ intronic (MiE_κ) and 3' (3'E_κ) 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_κ and 3'E_κ were deleted on both kappa alleles—were analyzed for κ rearrangement. Our findings indicate that these double-mutant B cells have essentially no κ rearrangement but do rearrange and express lambda. Therefore, these two kappa enhancers share essential roles in activating V_κJ_κ rearrangement. Our findings also indicate that the two κ enhancers play overlapping and distinct roles in the demethylation of κ in B cells.