Selective synergy of immunoglobulin enhancer elements in B-cell development: A characteristic of kappa light chain enhancers, but not heavy chain enhancers

We have examined the interactions of the enhancers of the kappa immunoglobulin light chain gene as well as the interactions of the intron, μ, and 3′ α enhancers of the heavy chain locus in mouse. We have observed that each of the kappa enhancers is very weak in comparison with the heavy chain intron enhancer. The mouse heavy chain 3′ α enhancer is relatively weak as well. However, two kappa enhancers together synergistically activate transcription of a luciferase reporter gene to a level that is roughly equivalent to the heavy chain μ enhancer. Additionally, dimerization of either kappa enhancer results in synergistic increases in transcription. This property of synergism appears to be confined to the enhancers of the kappa locus, as addition of the 3′ αE to μE containing constructs increases transcription only modestly, and neither heavy chain enhancer synergizes when dimerized. We have gone on to characterize some of the minimal requirements for synergism between the kappa enhancers and find that the KB and E2 sites are required, but not the E3 site. The implications of these results for the coordinate regulation of the heavy and light chain transcription are discussed.