Abstract
Purpose
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.
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Funding
This work was supported by the National Natural Science Foundation of China (81100158), National Basic Research Program of China (973 Program, 2007CB512000, 2007CB512005), and National Science and Technology Support Program (2011BAI11B00, 2011BAI11B23).
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Miao Yu, Shuang Wen and Min Wang contributed to the work equally.
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Yu, M., Wen, S., Wang, M. et al. TNF-α-Secreting B Cells Contribute to Myocardial Fibrosis in Dilated Cardiomyopathy. J Clin Immunol 33, 1002–1008 (2013). https://doi.org/10.1007/s10875-013-9889-y
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DOI: https://doi.org/10.1007/s10875-013-9889-y