The T-cell receptor β variable gene promoter is required for efficient Vβ rearrangement but not allelic exclusion

To investigate the role of promoters in regulating variable gene rearrangement and allelic exclusion, we constructed mutant mice in which a 1.2-kb region of the Vbeta13 promoter was either deleted (P13(-/-)) or replaced with the simian virus 40 minimal promoter plus five copies of Ga14 DNA sequences (P13(R/R)). In P13(-/-) mice, cleavage, rearrangement, and transcription of Vbeta13, but not the flanking Vbeta gene segments, were significantly inhibited. In P13(R/R) Mice, inhibition of Vbeta13 rearrangement was less severe and was not associated with any apparent reduction in Vbeta13 cleavage. Expression of a T-cell receptor (TCR) transgene blocked cleavages at the normal Vbeta13 -recombination signal sequence junction and Vbeta13 coding joint formation of both wild-type and mutant Vbeta13 alleles. However, a low level of aberrant Vbeta13 cleavage was consistently detected, especially in TCR transgenic P13(R/R) mice. These findings suggest that the variable gene promoter is required for promoting local recombination accessibility of the associated Vbeta gene segment. Although the promoter is dispensable for allelic exclusion, it appears to suppress aberrant Vbeta cleavages during allelic exclusion.