Abstract
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 μ heavy chain (HC) by testing whether it can participate in the formation of a preB cell receptor (preBCR), composed of the μ 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 (λ5−/−), transmembrane domain of μHC 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 μ-CT, histomorphometry and double calcein labeling. Both cortical and trabecular bone mass were significantly decreased in the femurs of the λ5 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 λ5−/− 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.
Highlights
In the bone marrow, B cell progenitors are found adjacent to the endosteum where osteoblasts, osteoclasts, and other bone elements reside [1]
In the course of our studies of early B cell development, we noticed that when we extracted bone marrow from both male and female λ5−/− mice at 12 weeks of age, their bones appeared more fragile than wild type, irrespective of gender
This led us to test whether the preB cell receptor (preBCR) was involved in bone homeostasis
Summary
B cell progenitors are found adjacent to the endosteum where osteoblasts, osteoclasts, and other bone elements reside [1]. In osteoclast impaired osteopetrotic mice the transition of proB to preB cell is obstructed [3]. IL-7R deficient mice, which exhibit a block at the preB cell stage, show increased bone mineral density [7]. Deficiency of Pax-5, a key transcription factor for preBCR expression, leads to a block at the proB cell stage [9] and increased numbers of osteoclasts [4, 10, 11]. Loss of early B cell factor, a transcription factor that controls preBCR expression [12], leads to a decreased osteoclast numbers and an increase in osteoblast numbers and bone formation [13]
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