Diversification of the TCR β Locus V_β Repertoire by CTCF

The architectural protein CTCF regulates the conformation and recombination of antigen receptor loci. To study the importance of CTCF in Tcrb locus repertoire formation, we created a conditional knockout mouse line that deletes Ctcf early during thymocyte development. We observed an incomplete block in thymocyte development at the double-negative to double-positive transition, resulting in greatly lowered thymic cellularity. The Tcrb repertoire was altered with a decrease in recombination of V_β gene segments in close proximity to a CTCF binding element (CBE), resulting in an overall repertoire that was skewed in favor of V_β gene segments with no nearby CBE. Therefore we show that CTCF functions to diversify the Tcrb repertoire.