Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19.
Kenneth B Hoehn, Palaniappan Ramanathan, Avraham Unterman, Tomokazu S Sumida, Hiromitsu Asashima, David A Hafler, Naftali Kaminski, Charles S Dela Cruz, Stuart C Sealfon, Alexander Bukreyev, Steven H Kleinstein
Author Information
Kenneth B Hoehn: Department of Pathology, Yale School of Medicine, New Haven, CT.
Palaniappan Ramanathan: Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, TX. ORCID
Avraham Unterman: Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT. ORCID
Tomokazu S Sumida: Department of Neurology, School of Medicine, Yale University, New Haven, CT. ORCID
Hiromitsu Asashima: Department of Neurology, School of Medicine, Yale University, New Haven, CT.
David A Hafler: Department of Neurology, School of Medicine, Yale University, New Haven, CT. ORCID
Naftali Kaminski: Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT. ORCID
Charles S Dela Cruz: Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT. ORCID
Stuart C Sealfon: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY. ORCID
Alexander Bukreyev: Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, TX.
Steven H Kleinstein: Department of Pathology, Yale School of Medicine, New Haven, CT; steven.kleinstein@yale.edu. ORCID
Protective immunity against COVID-19 likely depends on the production of SARS-CoV-2-specific plasma cells and memory B cells postinfection or postvaccination. Previous work has found that germinal center reactions are disrupted in severe COVID-19. This may adversely affect long-term immunity against reinfection. Consistent with an extrafollicular B cell response, patients with severe COVID-19 have elevated frequencies of clonally expanded, class-switched, unmutated plasmablasts. However, it is unclear whether B cell populations in individuals with mild COVID-19 are similarly skewed. In this study, we use single-cell RNA sequencing of B cells to show that in contrast to patients with severe COVID-19, subjects with mildly symptomatic COVID-19 have B cell repertoires enriched for clonally diverse, somatically hypermutated memory B cells ∼30 d after the onset of symptoms. This provides evidence that B cell responses are less disrupted in mild COVID-19 and result in the production of memory B cells.
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