A sex-biased imbalance between Tfr, Tph, and atypical B cells determines antibody responses in COVID-19 patients.
Jonas Nørskov SøndergaardJanyerkye TulyeuRyuya EdahiroYuya ShiraiYuta YamaguchiTeruaki MurakamiTakayoshi MoritaYasuhiro KatoHaruhiko HirataYoshito TakedaDaisuke OkuzakiShimon SakaguchiAtsushi KumanogohYukinori OkadaJames Badger WingPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
Sex-biased humoral immune responses to COVID-19 patients have been observed, but the cellular basis for this is not understood. Using single-cell proteomics by mass cytometry, we find disrupted regulation of humoral immunity in COVID-19 patients, with a sex-biased loss of circulating follicular regulatory T cells (cTfr) at a significantly greater rate in male patients. In addition, a male sex-associated cellular network of T-peripheral helper, plasma blasts, proliferating and extrafollicular/atypical CD11c + memory B cells was strongly positively correlated with neutralizing antibody concentrations and negatively correlated with cTfr frequency. These results suggest that sex-specific differences to the balance of cTfr and a network of extrafollicular antibody production-associated cell types may be a key factor in the altered humoral immune responses between male and female COVID-19 patients.
Keyphrases
- immune response
- regulatory t cells
- single cell
- sars cov
- dendritic cells
- rna seq
- end stage renal disease
- coronavirus disease
- toll like receptor
- newly diagnosed
- ejection fraction
- mass spectrometry
- peritoneal dialysis
- respiratory syndrome coronavirus
- stem cells
- high throughput
- bone marrow
- dengue virus
- functional connectivity
- zika virus
- network analysis
- chemotherapy induced