A sex-biased imbalance between Tfr, Tph, and atypical B cells determines antibody responses in COVID-19 patients
Jonas Nørskov Søndergaard, Janyerkye Tulyeu, Ryuya Edahiro, Yuya Shirai, Yuta Yamaguchi, Teruaki Murakami, Takayoshi Morita, Yasuhiro Kato, Haruhiko Hirata, Yoshito Takeda, Daisuke Okuzaki, Shimon Sakaguchi, Atsushi Kumanogoh, Yukinori Okada, James B. Wing
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 + 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.