摘要：SummaryClinically important broadly reactive B cells evolve during multiple infections, with B cells re-activated after secondary infection differing from B cells activated after a primary infection. Here we studied CD27highCD38highplasmablasts from patients with a primary or secondary dengue virus infection. Three transcriptionally and functionally distinct clusters were identified. The largest cluster 0/1 was plasma cell-related, with cells coding for serotype cross-reactive antibodies of the IgG1 isotype, consistent with memory B cell activation during an extrafollicular response. Cells in clusters 2 and 3 expressed low levels of antibody genes and high levels of genes associated with oxidative phosphorylation, EIF2 pathway, and mitochondrial dysfunction. Clusters 2 and 3 showed a transcriptional footprint of T cell help, in line with activation from naive B cells or memory B cells. Our results contribute to the understanding of the parallel B cell activation events that occur in humans after natural primary and secondary infection.Graphical abstractDisplay OmittedHighlights•CD27highCD38highplasmablasts from patients with dengue form three clusters•Clusters 0/1 express high levels, and more dengue-specific, antibodies•Clusters 0/1 are reminiscent of extrafollicular activation•Clusters 2 and 3 are metabolically active with an expression footprint of T cell helpImmunology; Cell biology; Functional aspects of cell biology; Systems biology
