The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential.

The B-lymphocyte potential of progenitor thymocytes and whether the thymus is colonized by common lymphocyte progenitor cells have been subjects of considerable debate. Herein, we have used limiting dilution analysis to determine the lineage potential of phenotypically defined subpopulations of CD4-CD8- double-negative thymocytes. Culture systems used showed single-hit kinetics and had a high plating efficiency for B-, myeloid, and natural killer cell development. The T-cell potential of sorted cells was confirmed by transferring cells to fetal thymus organ cultures. Our results indicate that the earliest population of CD117+ double-negative cells, although containing potent T-cell developmental potential and significant myeloid and natural killer potential, does not have any residual B-cell potential. Gene transcription analysis also indicated that these double-negative cells contained abundant T and myeloid, but not B cell-specific transcripts. The implications of these results within the context of current models of thymocyte development are discussed.