Lineage commitment in lymphopoiesis

The mechanisms controlling the commitment of hematopoietic progenitor cells to the lymphoid lineages are still mostly unknown. Recent findings indicat e that the earliest phase of B cell development may proceed in two steps. A t the onset of B-lymphopoiesis, the transcription factors E2A and EBF coord inately activate the B-cell-specific gene expression program, Subsequently, Pax5 appears to repress the promiscuous transcription of lineage-inappropr iate genes and thus commits progenitor cells to the B-lymphoid pathway by s uppressing alternative cell fates. B-lineage commitment by Pax5 seems to oc cur in a stochastic manner in the bone marrow, as indicated by the random a ctivation of only one of the two Pax5 alleles in early pro-B cells, In cont rast, loss- and gain-of-function analyses have implicated the Notch1 recept or in the specification of the T cell fate, which may thus be controlled by instructive signals in the thymus.