Frontiers in Immunology (Oct 2024)

BCR, not TCR, repertoire diversity is associated with favorable COVID-19 prognosis

  • Faith Jessica Paran,
  • Rieko Oyama,
  • Abdullah Khasawneh,
  • Tomohiko Ai,
  • Hendra Saputra Ismanto,
  • Aalaa Alrahman Sherif,
  • Dianita Susilo Saputri,
  • Chikako Ono,
  • Mizue Saita,
  • Satomi Takei,
  • Yuki Horiuchi,
  • Ken Yagi,
  • Yoshiharu Matsuura,
  • Yasushi Okazaki,
  • Yasushi Okazaki,
  • Kazuhisa Takahashi,
  • Kazuhisa Takahashi,
  • Daron M. Standley,
  • Yoko Tabe,
  • Yoko Tabe,
  • Toshio Naito,
  • Toshio Naito

DOI
https://doi.org/10.3389/fimmu.2024.1405013
Journal volume & issue
Vol. 15

Abstract

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IntroductionThe SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients.Materials and methodsIn this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages.ResultsExpanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, but represented only a small fraction of the total repertoire in all patients. In contrast, while deceased patients exhibited monoclonal B cell receptor (BCR) expansions without COVID-19 specificity, survivors demonstrated diverse and specific BCR clones. These findings suggest that neither TCR diversity nor BCR monoclonal expansions are sufficient for viral clearance and subsequent recovery. Differential gene expression analysis revealed that protein biosynthetic processes were enriched in survivors, but that potentially damaging mitochondrial ATP metabolism was activated in the deceased.ConclusionThis study underscores that BCR repertoire diversity, but not TCR diversity, correlates with favorable outcomes in COVID-19.

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