AUTHOR=Kuijper Lisan H. , Kreher Christine , Elias George , Claireaux Mathieu , Kerster Gius , Bos Amélie V. , Duurland Mariël C. , Konijn Veronique A. L. , Paul Alberta G. A. , de Jong Nina , de Jongh Rivka , Steenhuis Maurice , Garcia-Vallejo Juan J. , van Gils Marit J. , Kuijpers Taco W. , Eftimov Filip , Rispens Theo , van der Schoot C. Ellen , van Ham S. Marieke , ten Brinke Anja 

TITLE=Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1505719

DOI=10.3389/fimmu.2024.1505719

ISSN=1664-3224

ABSTRACT=IntroductionUpon infection, T cell-driven B cell responses in GC reactions induce memory B cells and antibody-secreting cells that secrete protective antibodies. How formation of specifically long-lived plasma cells is regulated via the interplay between specific B and CD4+ T cells is not well understood. Generally, antibody levels decline over time after clearance of the primary infection.MethodIn this study, convalescent individuals with stable RBD antibody levels (n=14, “sustainers”) were compared with donors (n=13) with the greatest antibody decline from a cohort of 132. To investigate the role of the cellular immune compartment in the maintenance of antibody levels, SARS-CoV-2-specific responses at 4 to 6 weeks post-mild COVID-19 infection were characterized using deep immune profiling.ResultsBoth groups had similar frequencies of total SARS-CoV-2-specific B and CD4+ T cells. Sustainers had fewer Spike-specific IgG+ memory B cells early after infection and increased neutralizing capacity of RBD antibodies over time, unlike the declining group. However, declining IgG titers correlated with lower frequency of Spike-specific CD4+ T cells.ConclusionThese data suggest that “sustainers” have unique dynamics of GC reactions, yield different outputs of terminally differentiating cells, and improve the quality of protective antibodies over time. This study helps identify factors controlling formation of long-lived PC and sustained antibody responses.