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Cell-nonautonomous hedgehog signaling promotes murine B lymphopoiesis from hematopoietic progenitors

Christopher L. Cooper, Richard R. Hardy, Michael Reth and Stephen Desiderio

Abstract

The role of hedgehog (Hh) signaling in B lymphopoiesis has remained unclear. We observed that proliferation of pro-B cells in stromal cocultures was impaired by inter-ruption of Hh signaling, prompting us to ask whether the target of Hh antagonism was intrinsic or extrinsic to the B lymphoid compartment. By conditional deletion of the pathway activator gene Smo we found that cell-autonomous Hh signaling is dispensable for B cell development, B lymphoid repopulation of bone marrow and humoral immune function. In contrast, depletion of Smo protein from stromal cells was associated with impaired generation of B lymphoid cells from hematopoietic stem progenitor cells (HSPC), while reciprocal removal of Smo from HSPC had no effect on production of B cell progenitors. Depletion of Smo from stromal cells was associated with coordinate downregulation of genes whose expression is associated with osteoblastoid identity and B lymphopoietic activity. Our results suggest that activity of the Hh pathway within stro-mal cells promotes B lymphopoiesis in a cell-nonautonomous fashion.

  • Submitted December 14, 2011.
  • Accepted April 10, 2012.