Background: CD11c +Tbet + B cells are enriched in autoimmunity and chronic infections and also expand on immune challenge in healthy individuals. CD11c +Tbet + B cells remain an enigmatic B-cell population because of their intrinsic heterogeneity. Objectives: We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-specific development and differentiation properties of 3 separate CD11c + B-cell subsets—age-associated B cells (ABCs), double-negative 2 (DN2) B cells, and activated naive B cells—and compared them to their canonical CD11c counterparts. Methods: Dynamics of the response of the 3 CD11c + B-cell subsets were assessed at SARS-CoV-2 vaccination in healthy donors by spectral flow cytometry. Distinct CD11c + B-cell subsets were functionally characterized by optimized in vitro cultures. Results: In contrast to a durable expansion of antigen-specific CD11c memory B cells over time, both ABCs and DN2 cells were strongly expanded shortly after second vaccination and subsequently contracted. Functional characterization of antibody-secreting cell differentiation dynamics revealed that CD11c +Tbet + B cells were primed for antibody-secreting cell differentiation compared to relevant canonical CD11c counterparts. Conclusion: Overall, CD11c +Tbet + B cells encompass heterogeneous subpopulations, of which primarily ABCs as well as DN2 B cells respond early to immune challenge and display a pre–antibody-secreting cell phenotype.

Original languageEnglish
Pages (from-to)689-699.e6
JournalJournal of allergy and clinical immunology
Issue number3
Early online date27 Feb 2023
Publication statusPublished - Sept 2023


  • CD11c Tbet atypical B cell
  • SARS-CoV-2 vaccination
  • activated naive
  • age-associated B cell
  • antibody-secreting cell differentiation
  • double negative 2

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