Disruption of the lineage restriction of TCRβ  gene rearrangements

Despite a common lymphoid recombinase, assembly of Ig genes is restricted to B cells, whereas TCR loci rearrange in T cells. Transcriptional promoters and enhancers are critical for the regulation of the recombination process. However, the specific function of such elements in conferring the lineage‐restriction of V(D)J recombination remains poorly understood. To gain further insights into the mechanism restricting TCRβ ‐chain rearrangements to T cells, we generated mice in which an 11 kb region — containing the β ‐chain constant region 2 and the TCRβ enhancer (Eβ ) — was replaced with the B cell specific Ig heavy‐chain enhancer (Eμ ). Unlike the simple Eμ to Eβ replacement, this mutation allowed significant levels of Dβ to Jβ as well as Vβ to DJβ rearrangements in both T and B cells. Although the lineage restriction was disrupted, TCRβ allelic exclusion was still efficient in mutated T cells. Together these results demonstrate that changes in the activity of regulatory elements located at the TCRβ constant regions are sufficient to redirect the recombination pattern of TCRβ variable gene segments.