title: Regulatory B cell is critical in bone union process through suppressing proinflammatory cytokines and stimulating Foxp3 in Treg cells.
abstract: Bone fractures may result in delayed union (DU) or non-union (NU) in some patients. Evidence suggests that the skewing of the immune system toward the proinflammatory type is a contributing factor. Because B cells were previously found to infiltrate the fracture healing site at abundant levels, we examined the regulatory B cells (Bregs) in DU/NU patients. In bone fracture patients with normal healing, the frequency of interleukin (IL)-10-expressing B cells was significantly upregulated in the early healing process (6 weeks post-surgery) and was downregulated later on (18 weeks post-surgery), whereas in DU/NU patients, the early upregulation of IL-10-expressing B cells was missing. The majority of IL-10-expressing B cells were concentrated in the IgM+CD27+fraction in both controls and patients. IgM+CD27+B cells effectively suppressed interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-2 expression from CD4+T cells, as well as IFN-γ and TNF-α expression from CD8+T cells. The IgM+CD27+B cell-mediated suppression was restricted to the sample from the early healing time point in controls, as the IgM+CD27+B cells from normal healing patients later on or from DU/NU patients did not present significant regulatory function. In addition, culturing of CD4+CD25+Tregs with IgM+CD27+B cells from controls at early healing time point resulted in higher Foxp3 expression, a function absent in controls at later time point, or in DU/NU patients. In conclusion, our results support a role of B cell-mediated regulation early during the bone healing process.
authors.affiliation: Department of Orthopedics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Guojing
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Yicun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Yunfan
authors.initials: Y
authors.lastname: Ti
authors.affiliation: Department of Orthopedics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Qian
mesh_terms: D060151:B-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D017102:Fracture Healing; D050723:Fractures, Bone / Q000276:immunology* / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: B cell; IL-10; bone union