A Limited Role for β-Selection During γδ T Cell Development

T cells belong to two distinct lineages expressing either αβ or γδ TCR. During αβ T cell development, it is clearly established that productive rearrangement at the TCR β locus in immature precursor cells leads to the expression of a pre-TCR complex. Signaling through the pre-TCR results in the selective proliferation and maturation of TCR β+ cells, a process that is known as β-selection. However, the potential role of β-selection during γδ T cell development is controversial. Whereas PCR-RFLP and sequencing techniques have provided evidence for a bias toward in-frame VDJβ rearrangements in γδ cells (consistent with β-selection), γδ cells apparently develop normally in mice that are unable to assemble a pre-TCR complex due to a deficiency in TCR β or pTα genes. In this report, we have directly addressed the physiologic significance of β-selection during γδ cell development in normal mice by quantitating intracellular TCR β protein in γδ cells and correlating its presence with cell cycle status. Our results indicate that β-selection plays a significant (although limited) role in γδ cell development by selectively amplifying a minor subset of γδ precursor cells with productively rearranged TCR β genes.