Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages

Claireaux, M.; Elias, G.; Kerster, G.; Kuijper, LH.; Duurland, MC.; Paul, AGA.; Burger, JA.; Poniman, M.; Olijhoek, W.; de Jong, N.; de Jongh, R.; Wynberg, E.; van Willigen, HDG.; Prins, M.; De Bree, GJ.; de Jong, MD.; Kuijpers, TW.; Eftimov, F.; van der Schoot, CE.; Rispens, T.; Garcia-Vallejo, JJ.; ten Brinke, A.; van Gils, MJ.; van Ham, SM.

doi:10.1101/2023.12.19.572339

Cited by 2 publications

References 67 publications

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Characterization of a heterogenous activated B cell compartment arising early after antigen exposure preceding long-lived memory B cell formation

Fernandez Blanco,

Kuijper,

Kummer

et al. 2024

Preprint

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Once formed, plasma cells and memory B cells (MBCs) are difficult to eradicate, posing a problem in the context of unwanted antibody responses. Characterizing early B cell differentiation stages after antigen encounter is thus crucial to target and prevent unwanted antibody formation. Here, we unravelled in-depth longitudinal antigen-specific B cell responses after SARS-CoV-2 mRNA vaccination in healthy individuals using multiparameter spectral flow cytometry. The early antigen-specific B cell response was dominated by spike-specific IgG+ CD27+ CD71+ activated B cells (ActBCs), previously assigned as germinal center-derived and DN2 extrafollicular B cells. Within the early IgG+ ActBC compartment, six distinct clusters were identified with specific contraction dynamics, whereby some of these clusters were more closely related to pre-ASCs and others more to long-lived MBCs. Some of the highly contracting ActBC clusters expressed CD11c, a marker previously used to define atypical B cells. The transient presence of different ActBC clusters could also be observed in total B cells when gated in an antigen-independent manner. Our results thus delineate the early stages of the antigen-specific B cell response, with a further dissection of the CD71+ ActBC compartment. Detection of ActBC clusters early after antigen encounter in total B cells opens avenues for future evaluation of their potential to serve as a proxy for antigen-reactive B cells in autoimmunity or other unwanted B cell responses. Keywords: B cell differentiation; CD11c+ Activated B cells; mRNA vaccination; immunological memory; germinal center.

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Characterization of a heterogenous activated B cell compartment arising early after antigen exposure preceding long-lived memory B cell formation

Fernandez Blanco,

Kuijper,

Kummer

et al. 2024

Preprint

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

Kuijper,

Kreher,

Elias

et al. 2024

Front. Immunol.

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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.

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Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages

Cited by 2 publications

References 67 publications

Characterization of a heterogenous activated B cell compartment arising early after antigen exposure preceding long-lived memory B cell formation

Characterization of a heterogenous activated B cell compartment arising early after antigen exposure preceding long-lived memory B cell formation

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

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