Early Decisions in Lymphoid Development

Recent research suggests that lymphoid progenitors in the bone marrow comprise a heterogeneous cell population. This population first loses megakaryocyte/erythroid, and then granulocyte/macrophage, potential before committing to lymphoid lineages. B and T cells can originate by way of different pathways that appear to be used with varying frequencies in the animal. In the bone marrow, B cell specification and commitment is driven by the concerted action of transcription factors and IL-7 signaling. In the thymus, multipotent progenitors become committed to the T-cell lineage through the action of Notch1. The activated intracellular form of Notch1 suppresses transcription factors that can instruct myeloid cell fates, thereby directly coupling extracellular signaling with changes in transcriptional networks. In conclusion, although a lot is known about B and T cell commitment, more work needs to be done to clarify the earliest steps in lymphoid specification.