title: Non-cell-autonomous hedgehog signaling promotes murine B lymphopoiesis from hematopoietic progenitors.
abstract: The role of hedgehog (Hh) signaling in B lymphopoiesis has remained unclear. We observed that the proliferation of pro-B cells in stromal cocultures was impaired by interruption of Hh signaling, prompting us to investigate whether the target of Hh antagonism was intrinsic or extrinsic to the B-lymphoid compartment. In the present study, using 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 the BM, and humoral immune function. In contrast, depletion of the Smo protein from stromal cells was associated with impaired generation of B-lymphoid cells from hematopoietic stem progenitor cells, whereas reciprocal removal of Smo from these cells had no effect on the production of B-cell progenitors. Depletion of Smo from stromal cells was associated with coordinate down-regulation of genes for which expression is associated with osteoblastoid identity and B-lymphopoietic activity. The results of the present study suggest that activity of the Hh pathway within stromal cells promotes B lymphopoiesis in a non-cell-autonomous fashion.
authors.affiliation: Department of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Cooper
authors.forename: Richard R
authors.initials: RR
authors.lastname: Hardy
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
authors.forename: Stephen
authors.initials: S
authors.lastname: Desiderio
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D017353:Gene Deletion; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D056724:Immunity, Humoral; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000072086:Smoothened Receptor; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor