CD27hiCD38hi plasmablasts are activated B cells of mixed origin with distinct function

Clinically important broadly reactive B cells evolve during multiple infections. The phenotype and function of B cells re-activated after secondary infection is different compared to B cells activated after a primary infection. Here we studied CD27highCD38high plasmablasts from patients with a primary or secondary dengue virus infection. Three transcriptionally and functionally distinct plasmablast clusters were identified. The largest cluster 0/1 was plasma cell-related and contained cells coding for virus serotype cross-reactive antibodies of the IgG1 isotype, consistent with memory B cell activation during an extrafollicular response. In contrast, 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, which we name T cell-dependent plasmablasts, showed a transcriptional footprint of T cell help, in line with activation from either naïve 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.EGA study EGAS00001005258