Lineage commitment in lymphopoiesis

✍ Scribed by Meinrad Busslinger; Stephen L Nutt; Antonius G Rolink

• Book ID: 104359045
• Publisher: Elsevier Science
• Year: 2000
• Tongue: English
• Weight: 188 KB
• Volume: 12
• Category: Article
• ISSN: 0952-7915
• DOI: 10.1016/s0952-7915(99)00065-5

✦ Synopsis

The mechanisms controlling the commitment of hematopoietic progenitor cells to the lymphoid lineages are still mostly unknown. Recent findings indicate that the earliest phase of B cell development may proceed in two steps. At the onset of B-lymphopoiesis, the transcription factors E2A and EBF coordinately activate the B-cell-specific gene expression program. Subsequently, Pax5 appears to repress the promiscuous transcription of lineage-inappropriate genes and thus commits progenitor cells to the B-lymphoid pathway by suppressing alternative cell fates. B-lineage commitment by Pax5 seems to occur in a stochastic manner in the bone marrow, as indicated by the random activation of only one of the two Pax5 alleles in early pro-B cells. In contrast, loss-and gain-of-function analyses have implicated the Notch1 receptor in the specification of the T cell fate, which may thus be controlled by instructive signals in the thymus.