Developmental plasticity of lymphocytes

Experimental perturbation of signaling or transcription factor networks has been used to study the developmental potential of lymphoid progenitors, lineage-committed precursors and mature lymphocytes. Common lymphoid progenitors and uncommitted pro-T cells can be efficiently diverted into myeloid or erythroid lineages by ectopic cytokine signaling or retroviral expression of the myeloid C/EBPα or erythroid GATA1 transcription factor. Forced C/EBPα expression furthermore induces direct transdifferentiation of immature thymocytes or B cells into macrophages. Notably, conditional inactivation of the B cell commitment factor Pax5 is sufficient to convert mature B cells into functional T cells via dedifferentiation to uncommitted progenitors. Together these experiments have uncovered an unanticipated developmental plasticity of lymphocytes, which may account for lineage switches observed in human malignancies.