Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow

Viable Lin(-) CD27(+) c-kit(Hi) Sca-1(Hi) GFP(+) cells recovered from heterozygous RAG1/GFP knockin mice progressed through previously defined stages of B, T, and NK cell lineage differentiation. In contrast to the GFP(-) cohort, there was minimal myeloid or erythroid potential in cells with an active RAG1 locus. Partial overlap with TdT(+) cells suggested that distinctive early lymphocyte characteristics are not synchronously acquired. Rearrangement of Ig genes initiates before typical lymphoid lineage patterns of gene expression are established, and activation of the RAG1 locus transiently occurs in a large fraction of cells destined to become NK cells. These early lymphocyte progenitors (ELP) are distinct from stem cells, previously described prolymphocytes, or progenitors corresponding to other blood cell lineages.