Open AccessMitochondrial regulation of acute extrafollicular B‐cell responses to COVID‐19 severity
Author(s) -
Cao Tianyu,
Liu Li,
To Kelvin KaiWang,
Lim ChunYu,
Zhou Runhong,
Ming Yue,
Kwan KaYi,
Yu Sulan,
Chan ChunYin,
Zhou Biao,
Huang Haode,
Mo Yufei,
Du Zhenglong,
Gong Ruomei,
Yat LukTsz,
Hung Ivan FanNgai,
Tam Anthony Raymond,
To WingKin,
Leung WaiShing,
Chik Thomas ShiuHong,
Tsang Owen TakYin,
Lin Xiang,
Song Youqiang,
Yuen KwokYung,
Chen Zhiwei
Publication year - 2022
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.1025
Subject(s) - immune system , immunology , pathogenesis , cytokine , asymptomatic , peripheral blood mononuclear cell , medicine , disease , t cell , biology , biochemistry , in vitro
Background Patients with COVID‐19 display a broad spectrum of manifestations from asymptomatic to life‐threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive. Methods We investigated a total of 137 APs infected with SARS‐CoV‐2. Patients were divided into mild and severe patient groups based on their requirement of oxygen supplementation. All blood samples from APs were collected within three weeks after symptom onset. Freshly isolated PBMCs were investigated for B cell subsets, their homing potential, activation state, mitochondrial functionality and proliferative response. Plasma samples were tested for cytokine concentration, and titer of Nabs, RBD‐, S1‐, SSA/Ro‐ and dsDNA‐specific IgG. Results While critically ill patients displayed predominantly extrafollicular B cell activation with elevated inflammation, mild patients counteracted the disease through the timely induction of mitochondrial dysfunction in B cells within the first week post symptom onset. Rapidly increased mitochondrial dysfunction, which was caused by infection‐induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID‐19 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease. Conclusion Our results reveal an immune mechanism that controls SARS‐CoV‐2‐induced detrimental B cell responses and COVID‐19 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development.