Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism

Lymphocyte enhancer factor-1 (LEF-1) is a member of the LEF-1/TCF family of transcription factors, which have been implicated in Wnt signaling and tum origenesis. LEF-1 was originally identified in pre-B and T cells, but its f unction in B lymphocyte development remains unknown. Here we report that LE F-1-deficient mice exhibit defects in pro-B cell proliferation and survival in vitro and in vivo. We further show that Lef1(-/-) pro-B cells display e levated levels of fas and c-myc transcription, providing a potential mechan ism for their increased sensitivity to apoptosis. Finally, we establish a l ink between Wnt signaling and normal B cell development by demonstrating th at Wnt proteins are mitogenic for pro-B cells and that this effect is media ted by LEF-1.