Atypical B cells consist of subsets with distinct functional profiles

Atypical B cells are a population of activated B cells that are commonly enriched in individuals with chronic immune activation, but are also part of a normal immune response to infection or vaccination. To better define the role of atypical B cells in the human adaptive immune response, we performed single-cell sequencing of transcriptomes, cell surface markers, and B cell receptors in individuals with chronic exposure to the malaria parasite Plasmodium falciparum, a condition known to lead to accumulation of circulating atypical B cells. We identified three previously uncharacterized populations of atypical B cells with distinct transcriptional and functional profiles, and observed marked differences among these three subsets in their ability to produce IgG upon T-cell-dependent activation. Our findings help explain the conflicting observations in prior studies regarding the function of atypical B cells and highlight their different roles in the adaptive immune response in chronic inflammatory conditions.