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Medientyp:
E-Artikel
Titel:
Non–cell-autonomous hedgehog signaling promotes murine B lymphopoiesis from hematopoietic progenitors
Beteiligte:
Cooper, Christopher L.;
Hardy, Richard R.;
Reth, Michael;
Desiderio, Stephen
Erschienen:
American Society of Hematology, 2012
Erschienen in:Blood
Sprache:
Englisch
DOI:
10.1182/blood-2011-12-397976
ISSN:
0006-4971;
1528-0020
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>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.</jats:p>