Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Christopher L. Cooper1,
  2. Richard R. Hardy2,
  3. Michael Reth3, and
  4. Stephen Desiderio1,*
  1. 1 Department of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States;
  2. 2 Fox Chase Cancer Center, Philadelphia, PA, United States;
  3. 3 BIOSS Center for Biological Signalling Studies, University of Freiburg, Dept of Molecular Immunology, Faculty of Biology, University of Freiburg and MPI of Immunobiology and Epigenetics, Freiburg, Germany
  1. * Corresponding author; email: sdesider{at}jhmi.edu

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.