Smoothened Signaling In The Mouse Osteoblastoid Lineage Is Required For Efficient B Lymphopoiesis

The stromal signals that promote B lymphopoiesis remain poorly understood. Hedgehog (Hh) signaling promotes B lymphopoiesis in a non-cell-autonomous fashion in vitro, and depletion of the Hh effector Smoothened (Smo) from stromal cells is associated with the loss of osteoblastoid markers. These observations suggested that Hh signaling in the osteoblastoid lineage promotes B lymphopoiesis in vivo. To test this, we employed a mouse model for conditional ablation of Smo in the osteoblastoid lineage. Depletion of Smo from osteoblastoid cells is associated with profound and selective reductions in the number and proportion of bone marrow B-lymphoid progenitors. Upon partial bone marrow ablation, mutant animals exhibit delayed repopulation of the B-lymphoid compartment after the early lymphoid progenitor stage. Primary osteoblasts from mutant mice are defective in supporting B lymphopoiesis in vitro, whereas hematopoietic progenitors from mutant mice exhibit normal differentiation. Weconclude that efficient B lymphopoiesis in vivo is dependent on the maintenance of Hh signaling in the osteoblastoid lineage.