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Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16976-81. doi: 10.1073/pnas.0802898105. Epub 2008 Oct 28.

Osteoblastic regulation of B lymphopoiesis is mediated by Gs{alpha}-dependent signaling pathways.

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  • 1Endocrine Unit and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.

Abstract

Osteoblasts play an increasingly recognized role in supporting hematopoietic development and recently have been implicated in the regulation of B lymphopoiesis. Here we demonstrate that the heterotrimeric G protein alpha subunit G(s)alpha is required in cells of the osteoblast lineage for normal postnatal B lymphocyte production. Deletion of G(s)alpha early in the osteoblast lineage results in a 59% decrease in the percentage of B cell precursors in the bone marrow. Analysis of peripheral blood from mutant mice revealed a 67% decrease in the number of circulating B lymphocytes by 10 days of age. Strikingly, other mature hematopoietic lineages are not decreased significantly. Mice lacking G(s)alpha in cells of the osteoblast lineage exhibit a reduction in pro-B and pre-B cells. Furthermore, interleukin (IL)-7 expression is attenuated in G(s)alpha-deficient osteoblasts, and exogenous IL-7 is able to restore B cell precursor populations in the bone marrow of mutant mice. Finally, the defect in B lymphopoiesis can be rescued by transplantation into a WT microenvironment. These findings confirm that osteoblasts are an important component of the B lymphocyte niche and demonstrate in vivo that G(s)alpha-dependent signaling pathways in cells of the osteoblast lineage extrinsically regulate bone marrow B lymphopoiesis, at least partially in an IL-7-dependent manner.

PMID:
18957542
PMCID:
PMC2579363
DOI:
10.1073/pnas.0802898105
[PubMed - indexed for MEDLINE]
Free PMC Article
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