Differential activation of transcription versus recombination of transgenic T cell receptor β variable region gene segments in B and T lineage cells

Abstract

We have tested the ability of the T cell receptor β (TCR-β) transcriptional enhancer (E(β)) to confer transcriptional activation and tissue-specific V(D)J recombination of TCR-β V, D, and J segments in a transgenic minilocus recombination substrate. We find that the minimal E(β) element, as previously shown for a DNA segment that contained the Eμ element, promotes a high level of substrate D to J(β) rearrangement in both B and T cells, but only promotes V(β) to DJ(β) rearrangement in T cells. Thus, both the E(μ) and E(β) elements similarly direct V(D)J recombination of this substrate in vivo, supporting a general role for transcriptional enhancers in the normal regulation of this rearrangement process. Surprisingly, however, we found that both the V(β) and DJ(β) portion of the constructs were transcribed in an enhancer-dependent fashion (conferred by either E(μ) or E(β)) in both B and T lineage cells, including normal precursor B cells propagated in culture. These findings indicate that, at least in some contexts, transcriptional activation, per se, is not sufficient to confer V(D)J recombinational accessibility to a substrate V gene segment.