# Robust effector memory features of human T-bethi B cells induced by repeated mRNA vaccination

## TL;DR

Repeated mRNA vaccination creates a special type of B cell that quickly produces virus-fighting antibodies, improving immune memory.

## Contribution

Identifies T-bethi B cells as a distinct, functionally potent subset induced by repeated mRNA vaccination.

## Key findings

- T-bethi B cells are marked by CD11c, FcRL5, and T-bet gene activity.
- These B cells rapidly become antibody-secreting cells with high neutralizing power.
- They show affinity maturation and contribute to early immune recall responses.

## Abstract

The heterogeneity of memory B cells in response to repetitive cognate antigen challenges remains to be fully elucidated. Here, we identified a transcriptionally distinct cluster of T-bethi B cells, among SARS-CoV-2 RBD-specific B cells in PBMCs from healthy individuals vaccinated with the BNT162b2 SARS-CoV-2 mRNA vaccine. Our findings indicate that T-bethi B cells can be defined by a combination of CD11c and FcRL5 receptors, and are distinguished by distinct gene regulatory networks associated with effector functions. Notably, these T-bethi B cells were affinity-matured and exhibited rapid differentiation into antibody-secreting cells (ASCs) producing neutralizing antibodies comparable to classical memory B cells, underscoring their role in early recall responses. Taken together, these findings illuminate the potent effector memory roles of T-bethi B cells in adaptive immunity following vaccinations.

•Repeated vaccination induces affinity-matured T-bethi B cells with effector traits•Vaccine-induced T-bethi B cells are defined by CD11c, FcRL5, and a T-bet gene network•T-bethi B cells rapidly form neutralizing antibody-secreting cells upon recall

Repeated vaccination induces affinity-matured T-bethi B cells with effector traits

Vaccine-induced T-bethi B cells are defined by CD11c, FcRL5, and a T-bet gene network

T-bethi B cells rapidly form neutralizing antibody-secreting cells upon recall

Immunology; Immune response; Virology