Deep profiling of B cells responding to various pathogens uncovers compartments in IgG memory B cell and antibody-secreting lineages.

Improving our understanding of B cell transition to memory B cells (MBCs) and antibody-secreting cells (ASCs) is crucial for clinical monitoring and vaccine strategies. To explore these dynamics, we compared prepandemic antigen responses (influenza hemagglutinin, respiratory syncytial virus fusion glycoprotein, and tetanus toxoid) with recently encountered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen responses in convalescent COVID-19 patients using spectral flow cytometry. Our analysis revealed the CD43+CD71+IgG+ activated B cell subset, highly enriched for SARS-CoV-2 specificities, as a juncture for ASC and MBC differentiation, with CD86+ phenotypically similar to ASCs and CD86- to IgG+ MBCs. Moreover, subpopulations within IgG+ MBCs were further identified based on CD73 and CD24 expression. Activated MBCs (CD73-/CD24lo) were predominantly SARS-CoV-2-specific, while resting MBCs (CD73+/CD24hi) recognized prepandemic antigens. A CD95- subcluster within resting MBCs accounted for over 40% of prepandemic-specific cells, indicating long-lasting memory. These findings advance our understanding of IgG+ MBC and ASC development stages, shedding light on the decision-making process guiding their differentiation.