Inhibition of T-cell receptor β-chain gene rearrangement by overexpression of the non-receptor protein tyrosine kinase p56^lck

The variable region genes of the T cell receptor (TCR) α and β chains are assembled by somatic recombination of separate germline elements. During thymocyte development, gene rearrangements display both an ordered progression, with β chain formation preceding α chain, and allelic exclusion, with each cell containing a single functional β chain rearrangement. Although considerable evidence supports the view that the individual loci are regulated independently, signaling molecules that may participate in controlling TCR gene recombination remain unidentified. Here we report that the lymphocyte-specific protein tyrosine kinase p56^lck, when overexpressed in developing thymocytes, provokes a reduction in Vβ-Dβ rearrangement while permitting normal juxtaposition of other TCR gene segments. Our data support a model in which p56^lck activity impinges upon a signaling process that ordinarily permits allelic exclusion at the β-chain locus.