Plasticity of atypical B cell composition and function in response to malaria

Abstract Atypical B cells are generated during a normal adaptive immune response, yet the role of these in protective immunity is still largely unknown. Here, we used chronic Plasmodium falciparum exposure as model to gain insight into function and potential heterogeneity atypical response infection. To this end, performed single-cell sequencing on circulating from malaria-experienced individuals. Based distinct gene expression signatures, identified three novel cell subsets. Each subset had an effector profile that translated one previously proposed roles for cells: i) quiescent ii) antigen-presenting or iii) antibody-secreting precursors. We differentially expressed surface markers allowed us track each by flow cytometry. observed relative abundance was influenced timing sample collection relation Additionally, our analysis revealed enrichment CXCR3+ adults compared children, suggesting further context age antigen stimulation. explore contribution malaria, antigen-tetramers identify parasite-specific cells. All subsets harbored antigen-specific decreased frequency absence exposure, confirming their active transient malaria immunity. Finally, preliminary results suggest differ ability secrete antibodies after stimulation, highlighting cellular functions National Institutes Health predoctoral fellowship F31AI169993 (RR) grant R35GM128938 (FA) R01AI153425 (EB)