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Publication : Disruption of the preB Cell Receptor Complex Leads to Decreased Bone Mass.

First Author  Khass M Year  2019
Journal  Front Immunol Volume  10
Pages  2063 PubMed ID  31552025
Mgi Jnum  J:281324 Mgi Id  MGI:6377743
Doi  10.3389/fimmu.2019.02063 Citation  Khass M, et al. (2019) Disruption of the preB Cell Receptor Complex Leads to Decreased Bone Mass. Front Immunol 10:2063
abstractText  In the bone marrow, preB cells are found adjacent to the bone endosteum where bone synthesizing osteoblast and bone resorbing osteoclasts reside. Although there is evidence of interactions between preB and bone cells, the factors that contribute to such interactions are poorly understood. A critical checkpoint for preB cell development assesses the integrity of the nascent immunoglobulin mu heavy chain (HC) by testing whether it can participate in the formation of a preB cell receptor (preBCR), composed of the mu HC and surrogate light chain (LC). In this work, we tested whether loss of preBCR components can affect bone synthesis. A panel of gene targeted mice with sequential blocks in preBCR formation or function [surrogate light chain component lambda 5 deleted (lambda5(-/-)), transmembrane domain of muHC deleted (IgM-mem(-/-)), and CD19 preBCR co-receptor deleted (CD19(-/-))] were evaluated for effects on postnatal bone synthesis. Postnatal bone mass was analyzed in 6 month old mice using mu-CT, histomorphometry and double calcein labeling. Both cortical and trabecular bone mass were significantly decreased in the femurs of the lambda5 and IgM-mem deficient mice. Histomorphometric analysis showed a decrease in the numbers of osteoblasts and osteoclasts in all three mutant strains. Double calcein labeling revealed a significant decrease in dynamic synthesis and mineralization of bone in lambda5(-/-) mice. Our data strongly suggest that interference with preBCR formation or function affects bone homeostasis independent of the presence or absence of mature B cells, and that components of the preBCR play important, and potentially distinct, roles in regulating adult bone mass.
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