Commitment to the B-lymphoid lineage depends on the transcription factor Pax5

The Pax5 gene encoding the B-cell-specific activator protein (BSAP) is expr essed within the haematopoietic system exclusively in the B-lymphoid lineag e, where it is required in vivo for progression beyond the pro-B-cell stage . However, Pax5 is not essential for in vitro propagation of pro-B cells in the presence of interleukin-ir and stromal cells. Here we show that pro-B cells lacking Pax5 are also incapable of in vitro B-cell differentiation un less Pax5 expression is restored by retroviral transduction, Pax5(-/-) pro- B cells ape not restricted in their lineage fate, as stimulation with appro priate cytokines induces them to differentiate into functional macrophages, osteoclasts, dendritic cells, granulocytes and natural killer cells. As ex pected far a clonogenic haematopoietic progenitor with lymphomyeloid develo pmental potential, the Pax5(-/-) pro-B cell expresses genes of different li neage-affiliated programmes, and restoration of Pax5 activity represses thi s lineage-promiscuous transcription. Pax5 therefore plays an essential role in B-lineage commitment by suppressing alternative lineage choices.