Phenotypic heterogeneity defines B cell responses to repeated SARS-CoV-2 exposures through vaccination and infection
Summary: Long-lived humoral memory is key to durable immunity against pathogens yet remains challenging to define due to heterogeneity among antigen-reactive B cells. We addressed this gap through longitudinal sampling over the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) m...
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| Language: | English |
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Elsevier
2025-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725003286 |
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| author | Lela Kardava James Lim Clarisa M. Buckner Felipe Lopes de Assis Xiaozhen Zhang Wei Wang Mattie L. Melnyk Omar El Merhebi Krittin Trihemasava I-Ting Teng Robin Carroll Yogita Jethmalani Mike Castro Bob C. Lin Lauren H. Praiss Catherine A. Seamon Peter D. Kwong Richard A. Koup Leonid Serebryannyy David C. Nickle Tae-Wook Chun Susan Moir |
| author_facet | Lela Kardava James Lim Clarisa M. Buckner Felipe Lopes de Assis Xiaozhen Zhang Wei Wang Mattie L. Melnyk Omar El Merhebi Krittin Trihemasava I-Ting Teng Robin Carroll Yogita Jethmalani Mike Castro Bob C. Lin Lauren H. Praiss Catherine A. Seamon Peter D. Kwong Richard A. Koup Leonid Serebryannyy David C. Nickle Tae-Wook Chun Susan Moir |
| author_sort | Lela Kardava |
| collection | DOAJ |
| description | Summary: Long-lived humoral memory is key to durable immunity against pathogens yet remains challenging to define due to heterogeneity among antigen-reactive B cells. We addressed this gap through longitudinal sampling over the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccinations with or without breakthrough infection. High-dimensional phenotypic profiling performed on ∼72 million B cells showed that receptor-binding domain (RBD) reactivity was associated with five distinct immunoglobulin G (IgG) B cell populations. Two expressed the activation marker CD71, both correlated with neutralizing antibodies, yet the one lacking the memory marker CD27 was induced by vaccination and blunted by infection. Two were resting memory populations; one lacking CD73 arose early and contributed to cross-reactivity; the other, expressing CD73, arose later and correlated with neutralizing antibodies. The fifth, a rare germinal center-like population, contributed to recall responses and was highly cross reactive. Overall, robust and distinct responses to booster vaccination overcame the superiority of hybrid immunity provided by breakthrough infection. |
| format | Article |
| id | doaj-art-494406ef96e148e2b97d0b917ef2970f |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-494406ef96e148e2b97d0b917ef2970f2025-08-20T03:09:01ZengElsevierCell Reports2211-12472025-04-0144411555710.1016/j.celrep.2025.115557Phenotypic heterogeneity defines B cell responses to repeated SARS-CoV-2 exposures through vaccination and infectionLela Kardava0James Lim1Clarisa M. Buckner2Felipe Lopes de Assis3Xiaozhen Zhang4Wei Wang5Mattie L. Melnyk6Omar El Merhebi7Krittin Trihemasava8I-Ting Teng9Robin Carroll10Yogita Jethmalani11Mike Castro12Bob C. Lin13Lauren H. Praiss14Catherine A. Seamon15Peter D. Kwong16Richard A. Koup17Leonid Serebryannyy18David C. Nickle19Tae-Wook Chun20Susan Moir21Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USAMonoceros Biosystems, San Diego, CA 29130, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USACritical Care Medicine Department, Clinical Center, NIH, Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAMonoceros Biosystems, San Diego, CA 29130, USA; Department of Global Health, University of Washington, Seattle, WA 98105, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA; Corresponding authorSummary: Long-lived humoral memory is key to durable immunity against pathogens yet remains challenging to define due to heterogeneity among antigen-reactive B cells. We addressed this gap through longitudinal sampling over the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccinations with or without breakthrough infection. High-dimensional phenotypic profiling performed on ∼72 million B cells showed that receptor-binding domain (RBD) reactivity was associated with five distinct immunoglobulin G (IgG) B cell populations. Two expressed the activation marker CD71, both correlated with neutralizing antibodies, yet the one lacking the memory marker CD27 was induced by vaccination and blunted by infection. Two were resting memory populations; one lacking CD73 arose early and contributed to cross-reactivity; the other, expressing CD73, arose later and correlated with neutralizing antibodies. The fifth, a rare germinal center-like population, contributed to recall responses and was highly cross reactive. Overall, robust and distinct responses to booster vaccination overcame the superiority of hybrid immunity provided by breakthrough infection.http://www.sciencedirect.com/science/article/pii/S2211124725003286CP: Immunology |
| spellingShingle | Lela Kardava James Lim Clarisa M. Buckner Felipe Lopes de Assis Xiaozhen Zhang Wei Wang Mattie L. Melnyk Omar El Merhebi Krittin Trihemasava I-Ting Teng Robin Carroll Yogita Jethmalani Mike Castro Bob C. Lin Lauren H. Praiss Catherine A. Seamon Peter D. Kwong Richard A. Koup Leonid Serebryannyy David C. Nickle Tae-Wook Chun Susan Moir Phenotypic heterogeneity defines B cell responses to repeated SARS-CoV-2 exposures through vaccination and infection Cell Reports CP: Immunology |
| title | Phenotypic heterogeneity defines B cell responses to repeated SARS-CoV-2 exposures through vaccination and infection |
| title_full | Phenotypic heterogeneity defines B cell responses to repeated SARS-CoV-2 exposures through vaccination and infection |
| title_fullStr | Phenotypic heterogeneity defines B cell responses to repeated SARS-CoV-2 exposures through vaccination and infection |
| title_full_unstemmed | Phenotypic heterogeneity defines B cell responses to repeated SARS-CoV-2 exposures through vaccination and infection |
| title_short | Phenotypic heterogeneity defines B cell responses to repeated SARS-CoV-2 exposures through vaccination and infection |
| title_sort | phenotypic heterogeneity defines b cell responses to repeated sars cov 2 exposures through vaccination and infection |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725003286 |
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