title: Loss of B cell regulatory function is associated with delayed healing in patients with tibia fracture.
abstract: The process of bone regeneration after fracture is a complex and well-orchestrated process usually requiring 3-12 weeks. A subset of patients, however, exhibit delayed healing time and even incomplete restoration of the normal bone structure. Although the precise mechanism is unknown, studies have shown that smurf1 may play a role during the process. Here, we sought to determine the involvement of the immune system in impaired bone healing. We found that immediately after fracture, the B-cell composition was shifted toward increased frequency of plasmablasts and decreased frequency of naïve B cells, reflecting higher inflammatory status. The percentage of CD19(+) CD24(+) CD38(+) regulatory B cells was also upregulated in response to bone fracture. The production of IL-10, a pivotal cytokine in regulatory B-cell function, was upregulated in all patients. Interestingly, the increase in IL-10 production was only sustained throughout the healing course in normal healing patients but not in delayed healing patients. Rather, delayed healing patients downregulated B-cell IL-10 secretion early and had reduced level of regulatory B-cell activity. Together, these data revealed a role of regulatory B cells in the endogenous bone regeneration process and an alternation in B-cell-mediated regulation in delayed healing patients.
authors: Department of Orthopedics, The 81st Hospital of PLA, Nanjing, Jiangsu, China.
authors: Shufeng
authors: S
authors: Yang
authors: Department of Radiotherapy, The 81st Hospital of PLA, Nanjing, Jiangsu, China.
authors: Wei
authors: W
authors: Ding
authors: Department of Spine Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Dapeng
authors: D
authors: Feng
authors: Department of Orthopedics, The 81st Hospital of PLA, Nanjing, Jiangsu, China.
authors: Haiyang
authors: H
authors: Gong
authors: Department of Orthopedics, The 81st Hospital of PLA, Nanjing, Jiangsu, China.
authors: Dongmei
authors: D
authors: Zhu
authors: Department of Orthopedics, The 81st Hospital of PLA, Nanjing, Jiangsu, China.
authors: Bin
authors: B
authors: Chen
authors: Department of Orthopedics, The 81st Hospital of PLA, Nanjing, Jiangsu, China.
authors: Jianmin
authors: J
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000502:physiology*; D001861:Bone Regeneration / Q000276:immunology / Q000502:physiology; D005260:Female; D017102:Fracture Healing / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D013978:Tibial Fractures / Q000276:immunology* / Q000503:physiopathology*; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10
keywords: B cell; IL-10; bone fracture