Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice

AbstractObjective: Todetect the abnormal distribution of B-lymphocytes between peripheral and bone marrow (BM) compartments and explore the mechanism of abnormal chemotaxis of B-lymphocytes in lupus subjects. Methods: The proportions of CXC chemokine receptor (CXCR)4+ B cells and CFDA-labeled MRL/lp...

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Main Authors: Wenjuan Zheng, Yu Tang, Mengwei Cheng, Cui Ma, Xiaoming Fei, Wei Shi
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Autoimmunity
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/08916934.2024.2319207
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author Wenjuan Zheng
Yu Tang
Mengwei Cheng
Cui Ma
Xiaoming Fei
Wei Shi
author_facet Wenjuan Zheng
Yu Tang
Mengwei Cheng
Cui Ma
Xiaoming Fei
Wei Shi
author_sort Wenjuan Zheng
collection DOAJ
description AbstractObjective: Todetect the abnormal distribution of B-lymphocytes between peripheral and bone marrow (BM) compartments and explore the mechanism of abnormal chemotaxis of B-lymphocytes in lupus subjects. Methods: The proportions of CXC chemokine receptor (CXCR)4+ B cells and CFDA-labeled MRL/lpr-derived B cells were detected by flow cytometry. The levels of CXC chemokine ligand (CXCL)12in peripheral blood (PB)were measured by ELISA. The migrated B cells to osteoblasts (OBs) was measured by transwell migration assay. The relative spatial position of B cells, OBs and CXCL12 was presented by Immunofluorescence assay. Results: Firstly, we found that the percentage of CXCR4+ B cells was lower in PB and higher in the BM from both MRL/lpr mice and patientswith Systemic lupus erythematosus (SLE). Secondly, OBs from MRL/lpr mice produced more CXCL12 than that from C57BL/6 mice. Besides, MRL/lpr-derived OBs demonstrated more potent chemotactic ability toward B-lymphocytes than control OBs by vitro an vivo. Additionally, more B-lymphocytes were found to co-localize with OBs within the periosteal zone of bone in MRL/lpr mice. Lastly, the percentages of CXCR4+B cells were found to be negatively correlated with serum Immunoglobulin (Ig) G concentration, moreover, BM CXCL12 levels were found to be positively correlated with SLE disease activity index Score and negatively correlated with serum Complement3 (C3) concentration. Conclusions: our results indicated that there is a shifted distribution of B-lymphocytes between BM and peripheral compartments in both SLE patients and MRL/lpr mice. Besides, the up-regulated levels of CXCL12 in OBs was indicated to contribute to the enhanced chemotactic migration and anchorage of B-lymphocytes to OBs.
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spelling doaj.art-7e5361c30717499c9940220889aad1fd2024-02-26T07:01:59ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2024-12-0157110.1080/08916934.2024.2319207Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr miceWenjuan Zheng0Yu Tang1Mengwei Cheng2Cui Ma3Xiaoming Fei4Wei ShiDepartment of Rheumatology and Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Rheumatology and Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Rheumatology and Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Rheumatology and Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Hematology, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaAbstractObjective: Todetect the abnormal distribution of B-lymphocytes between peripheral and bone marrow (BM) compartments and explore the mechanism of abnormal chemotaxis of B-lymphocytes in lupus subjects. Methods: The proportions of CXC chemokine receptor (CXCR)4+ B cells and CFDA-labeled MRL/lpr-derived B cells were detected by flow cytometry. The levels of CXC chemokine ligand (CXCL)12in peripheral blood (PB)were measured by ELISA. The migrated B cells to osteoblasts (OBs) was measured by transwell migration assay. The relative spatial position of B cells, OBs and CXCL12 was presented by Immunofluorescence assay. Results: Firstly, we found that the percentage of CXCR4+ B cells was lower in PB and higher in the BM from both MRL/lpr mice and patientswith Systemic lupus erythematosus (SLE). Secondly, OBs from MRL/lpr mice produced more CXCL12 than that from C57BL/6 mice. Besides, MRL/lpr-derived OBs demonstrated more potent chemotactic ability toward B-lymphocytes than control OBs by vitro an vivo. Additionally, more B-lymphocytes were found to co-localize with OBs within the periosteal zone of bone in MRL/lpr mice. Lastly, the percentages of CXCR4+B cells were found to be negatively correlated with serum Immunoglobulin (Ig) G concentration, moreover, BM CXCL12 levels were found to be positively correlated with SLE disease activity index Score and negatively correlated with serum Complement3 (C3) concentration. Conclusions: our results indicated that there is a shifted distribution of B-lymphocytes between BM and peripheral compartments in both SLE patients and MRL/lpr mice. Besides, the up-regulated levels of CXCL12 in OBs was indicated to contribute to the enhanced chemotactic migration and anchorage of B-lymphocytes to OBs.https://www.tandfonline.com/doi/10.1080/08916934.2024.2319207SLECXCL12B cellsbone marrowosteoblasts
spellingShingle Wenjuan Zheng
Yu Tang
Mengwei Cheng
Cui Ma
Xiaoming Fei
Wei Shi
Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice
Autoimmunity
SLE
CXCL12
B cells
bone marrow
osteoblasts
title Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice
title_full Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice
title_fullStr Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice
title_full_unstemmed Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice
title_short Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice
title_sort dysregulated cxcl12 expression in osteoblasts promotes b lymphocytes preferentially homing to the bone marrow in mrl lpr mice
topic SLE
CXCL12
B cells
bone marrow
osteoblasts
url https://www.tandfonline.com/doi/10.1080/08916934.2024.2319207
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