title: TNF-α-secreting B cells contribute to myocardial fibrosis in dilated cardiomyopathy.
abstract: OBJECTIVE
  Excessive inflammation responses mediated by CD4(+) T cells contributes to myocardial fibrosis in dilated cardiomyopathy (DCM) resulting from viral myocarditis. Recently, some scholars discovered that B cells harbored an abnormal pro-inflammatory capacity besides the production of autoantibodies. Thus, we aimed to explore whether and which type of B cells act on myocardial fibrosis in DCM.
  
  
  METHODS
  A total of 56 newly hospitalized DCM patients were studied, and among these, 17 patients accepted the gadolinium enhanced cardiovascular magnetic resonance imaging (MRI) for myocardial fibrosis evaluations.
  
  
  RESULTS
  B cell functions including the frequency and proliferation were significantly elevated in DCM patients. After screening the important cytokines including IL-1β, IL-6, IL-10, IL-17, TNF-α and TGF-β produced in these B cells by flow cytometry, we found that only the TNF-α-secreting B cells were obviously increased. Furthermore, the TNF-α protein secretion and mRNA levels were also enhanced in LPS-stimulated B cell isolated from DCM patients. In addition, 10 patients (59%) with increased TNF-α-secreting B cells showed late enhancement and boosted serum procollagen type III compared with the other 7 patients (41%) whose enhancement could not be detected. Moreover, the frequencies of TNF-α-secreting B cells were negatively correlated with LVEF and positively correlated with LVEDD, NT-proBNP and procollagen type III in all of the DCM patients.
  
  
  CONCLUSIONS
  Our study firstly suggested that TNF-α-secreting B cells were involved in myocardial fibrosis, which revealed the new pathogenic mechanism of B cells in DCM, and therapeutic targets against these cells might be valuable.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie-Fang Avenue 1277#, Wuhan 430022, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Shuang
authors.initials: S
authors.lastname: Wen
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Guo
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liao
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009202:Cardiomyopathies / Q000276:immunology / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000473:pathology; D048708:Cell Growth Processes / Q000276:immunology; D024061:Collagen Type III / Q000276:immunology; D005260:Female; D005355:Fibrosis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
chemical_list: D024061:Collagen Type III; D014409:Tumor Necrosis Factor-alpha
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