Volume 21, No 7, Jul 2011
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 21 Issue 7, July 2011: 1102-1115
ORIGINAL ARTICLES
Osteoclast activity modulates B-cell development in the bone marrow
Anna Mansour1,2, Adrienne Anginot3,4, Stéphane J C Mancini3,4, Claudine Schiff3,4, Georges F Carle1,2, Abdelilah Wakkach1,2,5 and Claudine Blin-Wakkach1,2,5
1CNRS, GEPITOS, UMR 6235, Faculté de Médecine, 06100 Nice, France
2Université de Nice Sophia Antipolis, 06000 Nice, France
3Centre d'Immunologie de Marseille Luminy; INSERM, CNRS, Parc Scientifique de Luminy, 13288 Marseille cedex 09, France
4Université de la M閐iterranée, Parc Scientifique de Luminy, 13288 Marseille cedex 09, France
5INSERM, UMR 576, H魀ital de l'Archet, 06202 Nice, France
Correspondence: Claudine Blin-Wakkach,(blin@unice.fr)
B-cell development is dependent on the interactions between B-cell 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 microenvironment 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.
Cell Research (2011) 21:1102-1115. doi:10.1038/cr.2011.21; published online 15 February 2011
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