AUTHOR=Besavilla Danica F. , Reusch Laura , Enriquez Josue , Schön Karin , Angeletti Davide 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 JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1243164 DOI=10.3389/fimmu.2023.1243164 ISSN=1664-3224 ABSTRACT=

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.