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Age-related functional decline of human B cells

Abstract

This study aimed to investigate the changes in B cell functional decline and antigen sensitization with aging using two Epstein Barr virus (EBV)-immortalized human B cell lines, one from a 22-year-old man (EBV-B young) and the other from a 65-year-old man (EBV-B old). The activity of senescence-associated β-galactosidase, a marker of cellular senescence, was enhanced in the EBV-B old cells compared with EBV-B young cells. Moreover, the levels of p16, p21, IL-6, TNF-α, and TGF-β1, which are senescence-associated secretary phenotypes, were also increased in EBV-B old cells. In vitro immunization of EBV-B cells with β-lactoglobulin further showed that EBV-B old cells had a reduced cell population of naïve B cells than that of EBV-B young cells. Furthermore, HLA-DR expression, which is important for antigen presentation, was decreased in the EBV-B old cells. Comparative microarray analysis between EBV-B young and old cells also showed decreased expression of antibody genes, such as those of the heavy chain and light chain (κ chain). These results suggest that cellular senescence and decreased gene expression are responsible, at least in part, for the decline in B cell function and antigen sensitization capacity with aging, which ultimately impairs the function of the acquired immune system.

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The data and materials that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank K. Yasuda (Cell Innovator, Fukuoka, Japan) for her assistance with the microarray analysis.

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The authors received no specific funding for this work.

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Correspondence to Tsukasa Fujiki.

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The authors have no relevant financial or non-financial interests to disclose.

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Fujiki, T., Matsumoto, SE., Kishihara, K. et al. Age-related functional decline of human B cells. Cytotechnology 74, 319–327 (2022). https://doi.org/10.1007/s10616-021-00513-z

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  • DOI: https://doi.org/10.1007/s10616-021-00513-z

Keywords

  • Antigen sensitization
  • Epstein Barr virus-immortalized B cell
  • Immune senescence
  • Senescence-associated secretory phenotype