Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infection
The influenza virus is a persistent burden on global health, with seasonal vaccines providing incomplete protection. CD4+ T cells help shape B cell and antibody responses; however, the selectivity of help and the effect on various antigen-specific B cell populations have not been fully elucidated. H...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1243164/full |
| _version_ | 1797730935594024960 |
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| author | Danica F. Besavilla Laura Reusch Josue Enriquez Karin Schön Davide Angeletti Davide Angeletti |
| author_facet | Danica F. Besavilla Laura Reusch Josue Enriquez Karin Schön Davide Angeletti Davide Angeletti |
| author_sort | Danica F. Besavilla |
| collection | DOAJ |
| description | The influenza virus is a persistent burden on global health, with seasonal vaccines providing incomplete protection. CD4+ T cells help shape B cell and antibody responses; however, the selectivity of help and the effect on various antigen-specific B cell populations have not been fully elucidated. Here, we studied the specificity, selectivity, and influence of nucleoprotein (NP) CD4+ T cells on the magnitude and quality of hemagglutinin (HA) and NP-specific B cells and antibody responses. We identified immunodominant peptides and showed that peptide immunization was sufficient to induce CD4+ cells with Th1 and Tfh phenotypes. Surprisingly, while preexisting CD4+ T cells enhanced the influx of total germinal center (GC) B cells in the mediastinal lymph node after infection, this was not reflected by an increase in the frequency of antigen-specific cells within the GC. Furthermore, we demonstrated that NP-specific help was able to accelerate the kinetics and magnitude of the Ab response for NP but not for HA. Overall, our results showed that pre-existing CD4+ T cells provide strong cognate help during immunization or infection to enhance Ab production but not antigen-specific GC or memory B cells. |
| first_indexed | 2024-03-12T11:51:19Z |
| format | Article |
| id | doaj.art-2feefe27354742879ab5c2f9ac6f5c37 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T11:51:19Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2feefe27354742879ab5c2f9ac6f5c372023-08-31T06:42:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12431641243164Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infectionDanica F. Besavilla0Laura Reusch1Josue Enriquez2Karin Schön3Davide Angeletti4Davide Angeletti5Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenSciLifeLab, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenThe influenza virus is a persistent burden on global health, with seasonal vaccines providing incomplete protection. CD4+ T cells help shape B cell and antibody responses; however, the selectivity of help and the effect on various antigen-specific B cell populations have not been fully elucidated. Here, we studied the specificity, selectivity, and influence of nucleoprotein (NP) CD4+ T cells on the magnitude and quality of hemagglutinin (HA) and NP-specific B cells and antibody responses. We identified immunodominant peptides and showed that peptide immunization was sufficient to induce CD4+ cells with Th1 and Tfh phenotypes. Surprisingly, while preexisting CD4+ T cells enhanced the influx of total germinal center (GC) B cells in the mediastinal lymph node after infection, this was not reflected by an increase in the frequency of antigen-specific cells within the GC. Furthermore, we demonstrated that NP-specific help was able to accelerate the kinetics and magnitude of the Ab response for NP but not for HA. Overall, our results showed that pre-existing CD4+ T cells provide strong cognate help during immunization or infection to enhance Ab production but not antigen-specific GC or memory B cells.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1243164/fullinfluenzaCD4+ T cellsB cellsantibodiesgerminal center |
| spellingShingle | Danica F. Besavilla Laura Reusch Josue Enriquez Karin Schön Davide Angeletti Davide Angeletti Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infection Frontiers in Immunology influenza CD4+ T cells B cells antibodies germinal center |
| title | Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infection |
| title_full | Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infection |
| title_fullStr | Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infection |
| title_full_unstemmed | Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infection |
| title_short | Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infection |
| title_sort | pre existing cd4 t cell help boosts antibody responses but has limited impact on germinal center antigen specific b cell frequencies after influenza infection |
| topic | influenza CD4+ T cells B cells antibodies germinal center |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1243164/full |
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