Heterogeneous Activated B Cell Compartments Arising Early and Transiently After SARS-CoV-2 Vaccination

Area of Science:

• Immunology
• Cell Biology
• Vaccinology

Background:

• B cell development post-antigen exposure in humans lacks clarity.
• Early B cell differentiation stages may offer biomarkers for immunity and targets for controlling antibody responses.

Purpose of the Study:

• To characterize antigen-specific B cell responses longitudinally after SARS-CoV-2 mRNA vaccination.
• To identify and define novel B cell subsets involved in the early immune response.

Main Methods:

• Longitudinal multiparameter spectral flow cytometry analysis of peripheral blood B cells.
• Characterization of antigen-specific B cell populations, including activated B cells (ActBCs) and memory B cells.

Main Results:

• Spike-specific IgG+ CD27+ CD71+ activated B cells (ActBCs) were dominant early after vaccination, with memory B cells prevalent at 6 months.
• Six novel ActBC clusters with distinct dynamics were identified within the IgG+ ActBC compartment.
• Some ActBC clusters showed sustained expansion, resembling memory B cells, while others rapidly contracted, with CD11c expression suggesting an extrafollicular origin.

Conclusions:

• Characterization of novel ActBC clusters provides a deeper understanding of B cell differentiation dynamics post-vaccination.
• These findings are crucial for dissecting complex B cell responses and understanding unwanted antibody production.