Pax5 is required for B cell lineage commitment
Pax5 is the master-regulator of B cell lineage commitment, as in its absence B cell progenitors, that are blocked at the pro-B cell stage, maintain a broad lympho-myeloid differentiation potential. Pax5 is expressed throughout B cell development where is plays a dual role in activating B cell specific genes while repressing genes associated with the stem cell, or alternative lineage, fates. Our studies aim to understand the molecular mechanism by which Pax5 achieves these dual goals. We have found that a crucial target of Pax5 repression is the receptor tyrosine kinase, Flt3. Flt3 is required for stem cell function and early B-lymphopoiesis. The repression of flt3 by Pax5 is an essential step in turning off the stem cell program to allow B cell commitment. Recent global gene expression analysis has identified approximately 200 additional Pax5 target genes that will shed more light on the function of this complex transcriptional regulator in B cell commitment. Further studies are aimed at understanding how Pax5 promotes B cell differentiation and interacts with Blimp-1 in plasma cell differentiation.
