The positional effect of Eβ on Vβ genes of TCRβ chain in the ordered rearrangement and allelic exclusion

Abstract

In the TCRbeta gene locus, the Vbeta, Dbeta and Jbeta gene segments are assembled in a tightly ordered manner. To investigate the positional effects of TCRbeta enhancer (Ebeta) on the recombination processes of the Vbeta genes, we utilized beta(LD) mice lacking 70% of the TCRbeta locus, leaving four Vbeta genes at the 5' side and, consequently, the Vbeta10 gene moves into the Ebeta regulatory region. In this mutant mouse, the Vbeta10 gene showed direct Vbeta-to-Dbeta and Vbeta-to-Jbeta recombination, although the Dbeta-to-Jbeta joining was still predominant. Interestingly, these two aberrant recombination processes were barely suppressed when beta(LD) mice were crossed with TCRbeta transgenic mice, whereas V(D)J recombination of the Vbeta10 gene was sufficiently suppressed. These results suggest that the positional effects of Ebeta on the Vbeta genes may enable the recombination potential to increase prior to Dbeta-to-Jbeta joining and that such aberrant recombination may be free from allelic suppression.