Pre-thymic transcription of TCR genes by adult murine bone marrow cells.

In the adult mouse, the earliest thymocytes are derived from bone marrow-resident T lymphocyte precursor (pre-T) cells that immigrate to the thymus. There they undergo maturation through a series of developmental steps that include rearrangement and expression of the TCR genes, positive and negative selection, and functional maturation. Although these intrathymic processes have been extensively characterized, little is known about the T cell-specific events that take place in the bone marrow microenvironment. Of particular interest are the events surrounding transcription and rearrangement of the various TCR chains that are required for functional TCR expression. We have previously reported the transcription of incompletely rearranged TCR beta genes in pre-T cell-containing fractions of adult bone marrow. Here we demonstrate that the TCR gamma chain genes are also transcriptionally active in these cells. Like the TCR beta transcripts, TCR gamma transcripts are sterile, originating from unrearranged gamma loci. Interestingly, both RAG-1 and RAG-2 transcripts were also detected in this cell fraction, suggesting that sterile TCR transcription might be dependent upon the presence of a functional recombinase system. However, both C beta and C gamma sterile transcripts could be detected from the same bone marrow cell population isolated from RAG-1 gene deficient mice. Therefore, the expression of TCR genes can initiate at the earliest stages of T cell development, prior to exposure to the thymic microenvironment, and a functional recombinase system is not required for the production of these sterile TCR transcripts.