Study on SARS-CoV-2-specific atypical memory B cells induced by vaccination exhibiting robust effector functions

Abstract

An elusive subset of memory B cells, known as atypical memory B cells, has been identified in various chronic inflammatory conditions and infections, with their specific role in the humoral immune response still under active investigation. In my study, I isolated RBD-specific B cells using fluorochrome-conjugated streptavidin tetramers, conducting LIBRA-seq and BCR-seq analyses. Kinetic data from PBMC samples of BNT162b2 vaccine recipients revealed a rising frequency of atypical memory B cells among RBD-specific B cells after each vaccine dose. Additionally, my in-depth analysis unveiled distinct gene regulatory networks, with T-bet as the most subset-specific, correlated with unique surface phenotypes and chemokine profiles. Gene Set Enrichment Analysis highlighted activation-prone pathways and in-vitro stimulation resulted in robust antibody-secreting cell differentiation and RBD-binding IgG antibody secretion compared with classical memory B cells, suggesting a potential role for these atypical memory B cells in future vaccine design and strategy against viral infections due to their effector memory features in cognate antigen challenges.