Cargando…

Loss of early B cell protein λ5 decreases bone mass and accelerates skeletal aging

The early B cell protein λ5 is an essential component of the surrogate light chain and the preB cell receptor (preBCR), which is critical for optimal B cell development. To investigate the effect of λ5 and/or B cells on bone acquisition over time, we developed a panel of J(H) (-/-) , λ5(-/-), J(H) (...

Descripción completa

Detalles Bibliográficos
Autores principales: Khass, Mohamed, Rashid, Harunur, Burrows, Peter D., Javed, Amjad, Schroeder, Harry W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516392/
https://www.ncbi.nlm.nih.gov/pubmed/36189270
http://dx.doi.org/10.3389/fimmu.2022.906649
_version_ 1784798699735482368
author Khass, Mohamed
Rashid, Harunur
Burrows, Peter D.
Javed, Amjad
Schroeder, Harry W.
author_facet Khass, Mohamed
Rashid, Harunur
Burrows, Peter D.
Javed, Amjad
Schroeder, Harry W.
author_sort Khass, Mohamed
collection PubMed
description The early B cell protein λ5 is an essential component of the surrogate light chain and the preB cell receptor (preBCR), which is critical for optimal B cell development. To investigate the effect of λ5 and/or B cells on bone acquisition over time, we developed a panel of J(H) (-/-) , λ5(-/-), J(H) (-/-) λ5(-/-), and wild-type (WT) BALB/c mice and then studied postnatal bone development and aging in these mice at one, six, twelve, and twenty-two months of age. The trabecular bone volume over total volume (BV/TV) in J(H) (-/-) mice was similar to WT mice at all ages. In contrast, at six months of age and thereafter, λ5(-/-) and J(H) (-/-) λ5(-/-) mice demonstrated a severe decrease in trabecular bone mass. Surprisingly, bone mass in six-month-old λ5(-/-) and J(H) (-/-) λ5(-/-) mice was similar to or even lower than in aged (twenty-two-months) WT mice, suggesting accelerated skeletal aging. The postnatal development and the acquisition of cortical bone mass in J(H) (-/-) λ5(-/-) mice were generally comparable to WT. However, J(H) (-/-) λ5(-/-) mice showed a significant decrease in cortical BV/TV at six- and twelve months of age. To examine the contribution of λ5 and B cells to postnatal bone synthesis, we separately transplanted whole bone marrow cells from J(H) (-/-) λ5(-/-) and WT mice into irradiated J(H) (-/-) λ5(-/-) and WT recipients. WT recipients of J(H) (-/-) λ5(-/-) marrow cells failed to show acquisition of trabecular bone mass, whereas transplanting WT marrow cells into J(H) (-/-) λ5(-/-) recipients led to the recovery of trabecular bone mass. Transfer of WT marrow cells into J(H) (-/-) λ5(-/-) mice promoted synthesis of new cortical and trabecular bone. Our findings indicate that λ5 plays a major role in preserving bone mass during postnatal development and skeletal aging which is distinct from its role in B cell development. The absence of both λ5 and B cells in J(H) (-/-) λ5(-/-) mice leads to delayed acquisition of cortical bone during postnatal development. Dissecting the mechanism(s) by which λ5 regulates bone homeostasis may provide new avenues for the treatment of age-related loss of bone mass and osteoporosis.
format Online
Article
Text
id pubmed-9516392
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95163922022-09-29 Loss of early B cell protein λ5 decreases bone mass and accelerates skeletal aging Khass, Mohamed Rashid, Harunur Burrows, Peter D. Javed, Amjad Schroeder, Harry W. Front Immunol Immunology The early B cell protein λ5 is an essential component of the surrogate light chain and the preB cell receptor (preBCR), which is critical for optimal B cell development. To investigate the effect of λ5 and/or B cells on bone acquisition over time, we developed a panel of J(H) (-/-) , λ5(-/-), J(H) (-/-) λ5(-/-), and wild-type (WT) BALB/c mice and then studied postnatal bone development and aging in these mice at one, six, twelve, and twenty-two months of age. The trabecular bone volume over total volume (BV/TV) in J(H) (-/-) mice was similar to WT mice at all ages. In contrast, at six months of age and thereafter, λ5(-/-) and J(H) (-/-) λ5(-/-) mice demonstrated a severe decrease in trabecular bone mass. Surprisingly, bone mass in six-month-old λ5(-/-) and J(H) (-/-) λ5(-/-) mice was similar to or even lower than in aged (twenty-two-months) WT mice, suggesting accelerated skeletal aging. The postnatal development and the acquisition of cortical bone mass in J(H) (-/-) λ5(-/-) mice were generally comparable to WT. However, J(H) (-/-) λ5(-/-) mice showed a significant decrease in cortical BV/TV at six- and twelve months of age. To examine the contribution of λ5 and B cells to postnatal bone synthesis, we separately transplanted whole bone marrow cells from J(H) (-/-) λ5(-/-) and WT mice into irradiated J(H) (-/-) λ5(-/-) and WT recipients. WT recipients of J(H) (-/-) λ5(-/-) marrow cells failed to show acquisition of trabecular bone mass, whereas transplanting WT marrow cells into J(H) (-/-) λ5(-/-) recipients led to the recovery of trabecular bone mass. Transfer of WT marrow cells into J(H) (-/-) λ5(-/-) mice promoted synthesis of new cortical and trabecular bone. Our findings indicate that λ5 plays a major role in preserving bone mass during postnatal development and skeletal aging which is distinct from its role in B cell development. The absence of both λ5 and B cells in J(H) (-/-) λ5(-/-) mice leads to delayed acquisition of cortical bone during postnatal development. Dissecting the mechanism(s) by which λ5 regulates bone homeostasis may provide new avenues for the treatment of age-related loss of bone mass and osteoporosis. Frontiers Media S.A. 2022-09-14 /pmc/articles/PMC9516392/ /pubmed/36189270 http://dx.doi.org/10.3389/fimmu.2022.906649 Text en Copyright © 2022 Khass, Rashid, Burrows, Javed and Schroeder https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Immunology
Khass, Mohamed
Rashid, Harunur
Burrows, Peter D.
Javed, Amjad
Schroeder, Harry W.
Loss of early B cell protein λ5 decreases bone mass and accelerates skeletal aging
title Loss of early B cell protein λ5 decreases bone mass and accelerates skeletal aging
title_full Loss of early B cell protein λ5 decreases bone mass and accelerates skeletal aging
title_fullStr Loss of early B cell protein λ5 decreases bone mass and accelerates skeletal aging
title_full_unstemmed Loss of early B cell protein λ5 decreases bone mass and accelerates skeletal aging
title_short Loss of early B cell protein λ5 decreases bone mass and accelerates skeletal aging
title_sort loss of early b cell protein λ5 decreases bone mass and accelerates skeletal aging
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516392/
https://www.ncbi.nlm.nih.gov/pubmed/36189270
http://dx.doi.org/10.3389/fimmu.2022.906649
work_keys_str_mv AT khassmohamed lossofearlybcellproteinl5decreasesbonemassandacceleratesskeletalaging
AT rashidharunur lossofearlybcellproteinl5decreasesbonemassandacceleratesskeletalaging
AT burrowspeterd lossofearlybcellproteinl5decreasesbonemassandacceleratesskeletalaging
AT javedamjad lossofearlybcellproteinl5decreasesbonemassandacceleratesskeletalaging
AT schroederharryw lossofearlybcellproteinl5decreasesbonemassandacceleratesskeletalaging