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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02063

Disruption of the preB cell receptor complex leads to decreased bone mass

 Mohamed Khass1, Harunur Rashid2, 3,  Peter D. Burrows2, 4,  Louis Bridges2, 5, Amjad Javed2, 3 and  Harry W. Schroeder1*
  • 1Medicine/Clinical Immunology and Rheumatology, University of Alabama at Birmingham, United States
  • 2University of Alabama at Birmingham, United States
  • 3Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Alabama at Birmingham, United States
  • 4Department of Microbiology, School of Medicine, University of Alabama at Birmingham, United States
  • 5Division of Clinical Immunology and Rheumatology, School of Medicine, University of Alabama at Birmingham, United States

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 mice with sequential gene targeted blocks in preBCR formation or function [surrogate light chain component lambda 5 deleted (λ5-/-), transmembrane domain of µHC deleted (IgM-mem-/-) and CD19 preBCR coreceptor deleted (CD19-/-)] were evaluated for effects on postnatal bone synthesis. Postnatal bone mass was analyzed in six 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.

Keywords: PreB cell receptor, surrogate light chain, Bone Development, B Cell Signaling, Adult bone mass

Received: 14 May 2019; Accepted: 15 Aug 2019.

Edited by:

Amy L. Kenter, University of Illinois at Chicago, United States

Reviewed by:

Kay L. Medina, Mayo Clinic, United States
Duane R. Wesemann, Brigham and Women's Hospital, Harvard Medical School, United States  

Copyright: © 2019 Khass, Rashid, Burrows, Bridges, Javed and Schroeder. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Harry W. Schroeder, University of Alabama at Birmingham, Medicine/Clinical Immunology and Rheumatology, Birmingham, 35294, Alabama, United States, hwsj@uab.edu