Osteoblastic regulation of B lymphopoiesis is mediated by Gsα-dependent signaling pathways
JY Wu, LE Purton, SJ Rodda, M Chen… - Proceedings of the …, 2008 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2008•National Acad Sciences
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 α subunit Gsα is required in cells of the
osteoblast lineage for normal postnatal B lymphocyte production. Deletion of Gsα 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 …
and recently have been implicated in the regulation of B lymphopoiesis. Here we
demonstrate that the heterotrimeric G protein α subunit Gsα is required in cells of the
osteoblast lineage for normal postnatal B lymphocyte production. Deletion of Gsα 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 …
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 α subunit Gsα is required in cells of the osteoblast lineage for normal postnatal B lymphocyte production. Deletion of Gsα 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 Gsα in cells of the osteoblast lineage exhibit a reduction in pro-B and pre-B cells. Furthermore, interleukin (IL)-7 expression is attenuated in Gsα-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 Gsα-dependent signaling pathways in cells of the osteoblast lineage extrinsically regulate bone marrow B lymphopoiesis, at least partially in an IL-7-dependent manner.
National Acad Sciences