Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets
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Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we used single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic human coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs.
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VH3-53 and VH3-66 are known to be enriched in RBD-binding B cells.
“Notably, both of these IGHV genes are known to be enriched in RBD-binding B cells (45, 46).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [46]
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mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern
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- Authors
- Dugan, H. L., Stamper, C. T., Li, L., Changrob, S., Asby, N. W., Halfmann, P. J., Zheng, N.-Y., Huang, M., Shaw, D. G., Cobb, M. S., Erickson, S. A., Guthmiller, J. J., Stovicek, O., Wang, J., Winkler, E. S., Madariaga, M. L., Shanmugarajah, K., Jansen, M. O., Amanat, F., Stewart, I., Utset, H. A., Huang, J., Nelson, C. A., Dai, Y.-N., Hall, P. D., Jedrzejczak, R. P., Joachimiak, A., Krammer, F., Diamond, M. S., Fremont, D. H., Kawaoka, Y., & Wilson, P. C.
- Affiliations
- University of Chicago (US)
- University of Wisconsin–Madison (US)
- Washington University in St. Louis (US)
- Icahn School of Medicine at Mount Sinai (US)
- Argonne National Laboratory (US)
- Corresponding author
- Wilson, Patrick C.
- ORCID
- Dugan, Haley L.
- Stamper, Christopher T.
- Li, Lei
- Changrob, Siriruk
- Asby, Nicholas W.
- Halfmann, Peter J.
- Zheng, Nai-Ying
- Shaw, Dustin G.
- Erickson, Steven A.
- Guthmiller, Jenna J.
- Stovicek, Olivia
- Wang, Jiaolong
- Winkler, Emma S.
- Madariaga, Maria Lucia
- Shanmugarajah, Kumaran
- Jansen, Maud O.
- Amanat, Fatima
- Utset, Henry A.
- Huang, Jun
- Nelson, Christopher A.
- Dai, Ya-Nan
- Hall, Paige D.
- Jedrzejczak, Robert P.
- Joachimiak, Andrzej
- Krammer, Florian
- Diamond, Michael S.
- Fremont, Daved H.
- Kawaoka, Yoshihiro
- Wilson, Patrick C.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 54
- Issue
- 6
- Pages
- 1290-1303.e7
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC8101792
- OpenAlex
- W3157116442
- Cited by
- 134
- References
- 66
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 20 · 2023: 24 · 2022: 34 · 2021: 29 · 2013: 1
- FWCI
- 8.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 372 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (F30 AI152327, T32 CA009594, R01 AI157155, U19AI057266, U19AI082724, U19AI109946)
- JPB Foundation
- Icahn School of Medicine at Mount Sinai
- Japan Agency for Medical Research and Development (R01 AI157155, F30 AI152327, JP19fk0108113, JP20fk0108272)
- Open Philanthropy Project (2020-215611)
- U.S. Department of Health and Human Services (HHSN272201700060C, HHSN272201400008C)
- University of Chicago (SCR_019196, SCR_017760)
- National Institute of Allergy and Infectious Diseases (75N93019C00062, 75N93019C00051, HHSN272201700060C)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- SARS-CoV-2, memory B cells, immunodominance, non-neutralizing antibodies, nucleocapsid protein, ORF8, spike protein, antibody evolution, pre-existing immunity, B cell maturation, monoclonal antibodies, COVID-19 pandemic
- MeSH terms
- COVID-19, SARS-CoV-2, Antibodies, Viral, Antibody Formation, B-Lymphocytes, Cross Reactions, Female, Humans, Immunologic Memory, Male, Neutralization Tests, Immunodominant Epitopes, Epitope Mapping, Computational Biology, Gene Expression Profiling, Host-Pathogen Interactions, Antibodies, Neutralizing, Single-Cell Analysis, High-Throughput Nucleotide Sequencing, Transcriptome, Spike Glycoprotein, Coronavirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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