CROSS-LINEAGE EXPRESSION OF IG-BETA (B29) IN THYMOCYTES - POSITIVE AND NEGATIVE GENE-REGULATION TO ESTABLISH T-CELL IDENTITY

Developmental commitment involves activation of lineage-specific genes , stabilization of a lineage-specific gene expression program, and per manent inhibition of inappropriate characteristics. To determine how t hese processes are coordinated in early T cell development, the expres sion of T and B lineage-specific genes was assessed in staged subsets of immature thymocytes, T lineage characteristics are acquired sequent ially, with germ-line T cell antigen receptor-beta transcripts detecte d very early, followed by CD3 epsilon and terminal deoxynucleotidyl tr ansferase, then pT alpha, and finally RAG1. Only RAG1 expression coinc ides with commitment. Thus, much T lineage gene expression precedes co mmitment and does not depend on it. Early in the course of commitment to the T lineage, thymocytes lose the ability to develop into B cells. To understand how this occurs, we also examined expression of well de fined B lineage-specific genes. Although lambda 5 and Ig-alpha are not expressed, the mu(0) and I mu transcripts from the unrearranged IgH l ocus are expressed early, in distinct patterns, then repressed just be fore RAG1 expression. By contrast, RNA encoding the B cell receptor co mponent Ig-beta was found to be transcribed in all immature thymocyte subpopulations and throughout most thymocyte differentiation. Ig-beta expression is down-regulated only during positive selection of CD4(+)C D8(-) cells. Thus several key participants in the B cell developmental program are expressed in non-B lineage-committed cells, and one is ma intained even through commitment to an alternative lineage, and repres sed only after extensive T lineage differentiation. The results show t hat transcriptional activation of ''lymphocyte-specific'' genes can oc cur in uncommitted precursors, and that T lineage commitment is a comp osite of distinct positive and negative regulatory events.