Distinct dynamics of antigen-specific induction and differentiation of different CD11c+Tbet+ B-cell subsets

• Published in: Journal of allergy and clinical immunology 2023-09, Vol.152 (3), p.689-699.e6
• Main Authors: Steuten, Juulke, Bos, Amélie V., Kuijper, Lisan H., Claireaux, Mathieu, Olijhoek, Wouter, Elias, George, Duurland, Mariel C., Jorritsma, Tineke, Marsman, Casper, Paul, Alberta G.A., Garcia Vallejo, Juan J., van Gils, Marit J., Wieske, Luuk, Kuijpers, Taco W., Eftimov, Filip, van Ham, S. Marieke, ten Brinke, Anja
• Format: Article
• Language: English
• Subjects: activated naive; age-associated B cell; antibody-secreting cell differentiation; B-Lymphocyte Subsets; CD11c+Tbet+ atypical B cell; Cell Differentiation; COVID-19; COVID-19 Vaccines; double negative 2; Humans; SARS-CoV-2; SARS-CoV-2 vaccination
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2023.02.020

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. 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. 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. 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. 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.