Biased Vβ Usage in Immature Thymocytes Is Independent of DJβ Proximity and pTα Pairing

During thymus development, the TCR β locus rearranges before the TCR α locus. Pairing of productively rearranged TCR β-chains with an invariant pTα chain leads to the formation of a pre-TCR and subsequent expansion of immature pre-T cells. Essentially nothing is known about the TCR Vβ repertoire in pre-T cells before or after the expression of a pre-TCR. Using intracellular staining, we show here that the TCR Vβ repertoire is significantly biased at the earliest developmental stage in which VDJβ rearrangement has occurred. Moreover (and in contrast to the VH repertoire in immature B cells), Vβ repertoire biases in immature T cells do not reflect proximity of Vβ gene segments to the DJβ cluster, nor do they depend upon preferential Vβ pairing with the pTα chain. We conclude that V gene repertoires in developing T and B cells are controlled by partially distinct mechanisms.