Distinct dynamics of antigen-specific induction and differentiation of different CD11c+Tbet+ B-cell subsets
Juulke Steuten, Amélie V. Bos, Lisan H Kuijper, Mathieu Claireaux, Wouter Olijhoek, George Elias, Mariël C Duurland, Tineke Jorritsma, Casper Marsman, A Paul, Juan J. García‐Vallejo, Marit J. van Gils, Luuk Wieske, Taco W. Kuijpers, Filip Eftimov, S. Marieke van Ham, Anja ten Brinke
Abstract
BackgroundCD11c+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.ObjectivesWe 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.MethodsDynamics 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.ResultsIn 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.ConclusionOverall, 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. 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.