title: Pathogenic conversion of regulatory B10 cells into osteoclast-priming cells in rheumatoid arthritis.
abstract: Regulatory B10 cells were functionally impaired in rheumatoid arthritis (RA), yet the mechanisms were unclear. B cells are recently recognized as important participants in osteoclastogenesis by producing RANKL. In this study, we investigated whether regulatory B10 cells could convert into RANKL-producing cells, thus impairing their immunosuppressive functions in RA and exacerbating the disease progression. Our results showed that human regulatory B10 cells could ectopically express RANKL. Under RA circumstance, RANKL-producing B10 cells expanded dramatically, partially induced by TNF-α. The frequencies of these cells were positively correlated with RA patient disease activities and tender joint counts, but negatively correlated with the frequencies of regulatory B10 cells. Strikingly, RANKL-producing B10 cells from RA patients, but not healthy individuals significantly promoted osteoclast differentiation and bone erosion in a paracrine and cell-cell contact-dependent manner. Moreover, these pathogenic RANKL-producing B10 cells declined while regulatory IL-10-producing B10 cells increased in RA patients with disease remission after therapy. Collectively, these results showed that in RA, regulatory B10 cells demonstrated the potential of converting into RANKL-producing cells, thus exacerbating osteoclast formation, bone destruction and disease progression. Modulating the status of B10 cells might provide novel therapeutic strategies for RA.
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
authors.forename: Fanlei
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Rheumatology and Immunology, the First People's Hospital of Yichang, China Three Gorges University, Yichang, China.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
authors.forename: Huaqun
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
authors.forename: Yingni
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, Peking University International Hospital, Beijing, China.
authors.forename: Lianjie
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. Electronic address: li99@bjmu.edu.cn.
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. Electronic address: jiayuan1023@sina.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jia
mesh_terms: D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D001323:Autoantibodies / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D016022:Case-Control Studies; D054338:Cell Transdifferentiation / Q000276:immunology; D000066630:Ectopic Gene Expression; D006801:Humans; D016130:Immunophenotyping; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha
keywords: Osteoclasts; RANKL; Regulatory B10 cells; Rheumatoid arthritis