Accumulation of synovial fluid CD19+CD24hiCD27+ B cells was associated with bone destruction in rheumatoid arthritis

Xiaofeng Guo,Huifang Zhang,Chongling Sun,Shulin Song,Hongjiang Liu,Kai Wang,Jing Zheng,Min Su,Xiangjun Cui,Ming Li,Tingting Xu,Ke Zheng

doi:10.1038/s41598-020-71362-7

Xiaofeng Guo, Huifang Zhang + Show 10 more

Open Access

https://doi.org/10.1038/s41598-020-71362-7

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Abstract

Regulatory CD19+CD24hiCD27+ B cells were proved to be numerically decreased and functionally impaired in the peripheral blood (PB) from rheumatoid arthritis (RA), with the potential of converting into osteoclast-priming cells. However, the distribution and function of CD19+CD24hiCD27+ B cells in RA synovial fluid (SF) were unclear. In this study, we investigated whether RA SF CD19+CD24hiCD27+ B cells were increased and associated with bone destruction. We found that the proportion of RA SF CD19+CD24hiCD27+ B cells was increased significantly, and was positively correlated with swollen joint counts, tender joint counts and disease activity. CXCL12, CXCL13, CCL19 contributed to the recruitment of CD19+CD24hiCD27+ B cells in RA SF. Notably, CD19+CD24hiCD27+ B cells in the SF from RA expressed significantly more RANKL compared to OA and that in the PB from RA. Critically, RA CD19+CD24hiCD27+ B cells promoted osteoclast (OC) differentiation in vitro, and the number of OCs was higher in cultures with RA SF CD19+CD24hiCD27+ B cells than in those derived from RA PB. Collectively, these findings revealed the accumulation of CD19+CD24hiCD27+ B cells in SF and their likely contribution to joint destruction in RA. Modulating the status of CD19+CD24hiCD27+ B cells might provide novel therapeutic strategies for RA.

Highlights

Regulatory CD19+CD24hiCD27+ B cells were proved to be numerically decreased and functionally impaired in the peripheral blood (PB) from rheumatoid arthritis (RA), with the potential of converting into osteoclast-priming cells
We have shown that C D19+CD24hiCD27+ B cell numbers were higher in RA synovial fluid (SF) than that in OA SF and RA PB
The percentage of RA SF CD19+CD24hiCD27+ B cells was positively correlated with swollen joint counts, tender joint counts, disease activity score in 28 joints (DAS28) and Sharp/van der Heijde score (SHS)

Summary

Introduction

Regulatory CD19+CD24hiCD27+ B cells were proved to be numerically decreased and functionally impaired in the peripheral blood (PB) from rheumatoid arthritis (RA), with the potential of converting into osteoclast-priming cells. RA CD19+CD24hiCD27+ B cells promoted osteoclast (OC) differentiation in vitro, and the number of OCs was higher in cultures with RA SF CD19+CD24hiCD27+ B cells than in those derived from RA PB These findings revealed the accumulation of CD19+CD24hiCD27+ B cells in SF and their likely contribution to joint destruction in RA. Studies of RANKL production in RA indicated that synovial fibroblasts and activated T cells produce excess RANKL and may contribute to osteoclastic bone r esorption[6,7,8]. Our previous study has shown that PB C D19+CD24hiCD27+ B cells have the potential of converting into RANKLproducing cells in RA patients[18] These findings highlight the important role of B cells in modulating bone. Characteristics of CD19+CD24hiCD27+ B cells in RA patient synovial fluids remain unclear

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