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

## TL;DR

This study identifies new types of activated B cells that appear briefly after SARS-CoV-2 vaccination, offering insights into immune responses and potential biomarkers.

## Contribution

The study identifies and characterizes novel activated B cell clusters with distinct contraction dynamics after SARS-CoV-2 vaccination.

## Key findings

- Spike-specific IgG+ CD27+ CD71+ activated B cells dominate the early B cell response after SARS-CoV-2 vaccination.
- Some activated B cell clusters persist and resemble memory B cells, while others expand and then contract rapidly.
- Certain transient B cell clusters express CD11c, suggesting an extrafollicular origin.

## Abstract

In humans, the stages and dynamics of B cell development after antigen encounter remain unclear. Identifying early B cell differentiation stages could reveal biomarkers for humoral immunity and potential targets to prevent unwanted antibody responses. We characterized antigen‐specific B cell responses longitudinally after SARS‐CoV‐2 mRNA vaccination using multiparameter spectral flow cytometry. Spike‐specific IgG+ CD27+ CD71+ activated B cells (ActBCs), presumed to be germinal center‐derived and IgG+ DN2 extrafollicular B cells, dominated the early antigen‐specific B cell response, while memory B cells were the main population 6 months after vaccination. Within the IgG+ ActBC compartment, we delineated six novel clusters with specific contraction dynamics. Following the second vaccination, certain ActBC clusters displayed sustained expansion over time, being phenotypically similar to memory B cells, while others strongly expanded and subsequently contracted. Several of the rapidly contracting ActBC clusters expressed CD11c, a defining marker for atypical B cells, suggesting a possible extrafollicular origin of these clusters. The transient presence of heterogeneous ActBC clusters was also observed for total B cells when gated in an antigen‐independent manner. Characterization of novel ActBC clusters early after antigen encounter helps delineate and dissect the complexity of B cell differentiation, which is vital for understanding unwanted B cell responses.

Characterization of the early antigen‐specific B cell response post‐SARS‐CoV‐2 vaccination reveals novel activated B cell clusters, showing different phenotypes and contraction dynamics. Some short‐lived activated B cells expressed both CD71 and the extrafollicular marker CD11c. These results advance our understanding of B‐cell differentiation regulation and biomarker potential.