Human naïve B cells show evidence of anergy and clonal redemption following vaccination
Abstract In an era of predicted emerging pandemics, the production of effective vaccines may require an in-depth understanding of the biology of human naive B (BN) cells. Here we provide evidence that the majority of BN cells expressed CD73, an ecto-5’-nucleotidase often associated with immune cell...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01133-w |
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| author | Brian L. P. Dizon Prasida Holla Evan C. Mutic Paul Schaughency Susan K. Pierce |
| author_facet | Brian L. P. Dizon Prasida Holla Evan C. Mutic Paul Schaughency Susan K. Pierce |
| author_sort | Brian L. P. Dizon |
| collection | DOAJ |
| description | Abstract In an era of predicted emerging pandemics, the production of effective vaccines may require an in-depth understanding of the biology of human naive B (BN) cells. Here we provide evidence that the majority of BN cells expressed CD73, an ecto-5’-nucleotidase often associated with immune cell suppression, and demonstrated features of anergy, including an IgMlowIgD+ surface phenotype, reduced calcium flux in response to IgM crosslinking, and increased PTEN expression. Analysis of antibody sequences encoded by the inherently autoreactive VH4-34 heavy chain produced by plasmablasts seven days following influenza vaccination showed that in younger but not in older individuals, anergic BN cells provided a reservoir of B cells capable of responding to vaccination by somatic mutation, resulting in diversification and loss of autoreactivity. These results suggest that effective human vaccines may require the ability to awaken or ‘redeem’ anergic BN cells that can be repurposed to participate in pathogen-specific responses. |
| format | Article |
| id | doaj-art-162b623264d746a2a5cbe9d3f779e5f7 |
| institution | OA Journals |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-162b623264d746a2a5cbe9d3f779e5f72025-08-20T01:52:03ZengNature Portfolionpj Vaccines2059-01052025-05-0110111410.1038/s41541-025-01133-wHuman naïve B cells show evidence of anergy and clonal redemption following vaccinationBrian L. P. Dizon0Prasida Holla1Evan C. Mutic2Paul Schaughency3Susan K. Pierce4Rheumatology Fellowship Training Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthRyan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of MedicineLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of HealthIntegrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract In an era of predicted emerging pandemics, the production of effective vaccines may require an in-depth understanding of the biology of human naive B (BN) cells. Here we provide evidence that the majority of BN cells expressed CD73, an ecto-5’-nucleotidase often associated with immune cell suppression, and demonstrated features of anergy, including an IgMlowIgD+ surface phenotype, reduced calcium flux in response to IgM crosslinking, and increased PTEN expression. Analysis of antibody sequences encoded by the inherently autoreactive VH4-34 heavy chain produced by plasmablasts seven days following influenza vaccination showed that in younger but not in older individuals, anergic BN cells provided a reservoir of B cells capable of responding to vaccination by somatic mutation, resulting in diversification and loss of autoreactivity. These results suggest that effective human vaccines may require the ability to awaken or ‘redeem’ anergic BN cells that can be repurposed to participate in pathogen-specific responses.https://doi.org/10.1038/s41541-025-01133-w |
| spellingShingle | Brian L. P. Dizon Prasida Holla Evan C. Mutic Paul Schaughency Susan K. Pierce Human naïve B cells show evidence of anergy and clonal redemption following vaccination npj Vaccines |
| title | Human naïve B cells show evidence of anergy and clonal redemption following vaccination |
| title_full | Human naïve B cells show evidence of anergy and clonal redemption following vaccination |
| title_fullStr | Human naïve B cells show evidence of anergy and clonal redemption following vaccination |
| title_full_unstemmed | Human naïve B cells show evidence of anergy and clonal redemption following vaccination |
| title_short | Human naïve B cells show evidence of anergy and clonal redemption following vaccination |
| title_sort | human naive b cells show evidence of anergy and clonal redemption following vaccination |
| url | https://doi.org/10.1038/s41541-025-01133-w |
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