A sex-biased imbalance between Tfr, Tph, and atypical B cells determines antibody responses in COVID-19 patients.

Søndergaard, Jonas Nørskov; Tulyeu, Janyerkye; Edahiro, Ryuya; Shirai, Yuya; Yamaguchi, Yuta; Murakami, Teruaki; Morita, Takayoshi; Kato, Yasuhiro et al. · Proc Natl Acad Sci U S A · 2023

basic_science · Level V

Where this comes from

Abstract

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<sup>+</sup> 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.

Medical subject headings