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The Role of B Cells in Regulation of Th Cell Differentiation in Coxsackievirus B3–Induced Acute Myocarditis

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Abstract

Viral myocarditis (VMC) is the major cause of sudden death in adolescents. To date, no effective treatment has been identified for VMC. Studies have shown that T helper (Th) cells such as Th1, Th2, Th17, and Th22 cells are involved in the pathogenesis of VMC. However, the role of B cells and their impact on Th cells in VMC is unclear. In this study, we investigated the role of B cells in Th cell differentiation in myocardial damage in an animal model of VMC. C57BL/6 mice were infected with Coxsackievirus B3 (CVB3) intraperitoneally or injected with phosphate-buffered saline as a control condition. At day 7, samples from these mice were analyzed by histology, ELISA, flow cytometry, and gene expression assays. We found that TNF-α-, IL-6-, and IL-17-producing B cell numbers were significantly increased, while IL-4-producing B cell population was significantly reduced in acute VMC. Furthermore, we performed B cell knockout (BKO), SCID, and SCID+B cells reconstitution experiments. We found that BKO alleviated the cardiac damage following CVB3 infection, may hamper the differentiation of Th1 and Th17 cells, may promote the differentiation of Th2 cells, and proved ineffective for the differentiation of Th22 cells. In contrast, SCID+B cells reconstitution experiment exacerbated the cardiac damage. Ex vivo studies further revealed that B cells promote the differentiation of Th1 and Th17 cells and inhibit the differentiation of Th2 cells. Our study shows that B cells are activated and have strong abilities of antigen presentation and producing cytokines in VMC; B cells not only play a pathogenic role in VMC independent of T cells but also promote Th1 and Th17 cell differentiation, and hamper Th2 cell differentiation in VMC.

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Funding

This work was supported by the National Natural Science Foundation of China (81670345).

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Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, People’s Republic of China

    Zhihong Cen, Yong Li, Bin Wei, Weifeng Wu, Yanlan Huang & Jing Lu

  2. Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Collaborative Innovation Center for Biomedicine & Guangxi Key Laboratory of Regenerative Medicine, Center for Translational Medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China

    Yong Li, Bin Wei, Weifeng Wu & Yanlan Huang

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  1. Zhihong Cen
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  5. Yanlan Huang
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Contributions

Zhihong Cen carried out experiments and prepared the manuscript. Yong Li and Bin Wei analyzed the experimental results. Weifeng Wu and Yanlan Huang conceived, designed, coordinated the study, and reviewed the manuscript. Jing Lu carried out data collection. All authors read and approved the final version of the manuscript.

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Correspondence to Weifeng Wu or Yanlan Huang.

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This study was performed with the approval of Guangxi Medical University Animal Ethics Committee. All animal procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85–23).

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Cen, Z., Li, Y., Wei, B. et al. The Role of B Cells in Regulation of Th Cell Differentiation in Coxsackievirus B3–Induced Acute Myocarditis. Inflammation 44, 1949–1960 (2021). https://doi.org/10.1007/s10753-021-01472-5

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  • DOI: https://doi.org/10.1007/s10753-021-01472-5

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