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Osteoclast activity modulates B-cell development in the bone marrow
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Osteoclast activity modulates B-cell development in the bone marrow
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Osteoclast activity modulates B-cell development in the bone marrow
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Journal Article
Osteoclast activity modulates B-cell development in the bone marrow
2011
Overview
B-cell development is dependent on the interactions between B-ceU precursors and bone marrow stromal cells, but the role of osteoclasts （OCLs） in this process remains unknown. B lymphocytopenia is a characteristic of osteopetrosis, suggesting a modulation of B lymphopoiesis by OCL activity. To address this question, we first rescued OCL function in osteopetrotic oc/oc mice by dendritic cell transfer, leading to a restoration of both bone phenotype and B-cell development. To further explore the link between OCL activity and B lymphopoiesis, we induced osteopetrosis in normal mice by injections of zoledronic acid （ZA）, an inhibitor of bone resorption. B-cell number decreased specifically in the bone marrow of ZA-treated mice. ZA did not directly affect B-cell differentiation, proliferation and apoptosis, but induced a decrease in the expression of CXCL12 and IL-7 by stromal cells, associated with reduced osteoblastic engagement. Equivalent low osteoblastic engagement in oc/oc mice confirmed that it resulted from the reduced OCL activity rather than from a direct effect of ZA on osteoblasts. These dramatic alterations of the bone mieroenvironment were disadvantageous for B lymphopoiesis, leading to retention of B-cell progenitors outside of their bone marrow niches in the ZA-induced osteopetrotic model. Altogether, our data revealed that OCLs modulate B-cell development in the bone marrow by controlling the bone microenvironment and the fate of osteoblasts. They provide novel basis for the regulation of the retention of B cells in their niche by OCL activity.
Publisher
Nature Publishing Group,CCSD,Nature Publishing Group UK
Subject
/ Animals
/ B-Lymphocytes - drug effects
/ Biomedical and Life Sciences
/ Bone and Bones - drug effects
/ Bone Density Conservation Agents - pharmacology
/ Bone Marrow Cells - cytology
/ Bone Marrow Cells - drug effects
/ Bone Marrow Cells - metabolism
/ B细胞
/ Cell Proliferation - drug effects
/ Chemokine CXCL12 - metabolism
/ Diphosphonates - pharmacology
/ Female
/ Lymphopoiesis - drug effects
/ Mice
/ Original
/ Osteopetrosis - chemically induced
/ Stromal Cells - drug effects
/ 小鼠骨髓
/ 成骨细胞
/ 活性调节
/ 破骨细胞
/ 诱导表达
/ 骨吸收抑制剂
/ 骨髓基质干细胞
ISBN
0002923229000
