CD27 hi CD38 hi 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 during secondary infection is different compared to B cells activated after a primary infection. Here we studied CD27high CD38high 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 also showed a transcriptional footprint of T cell help, in line with activation from either naive B cells or memory B cells in the context of a germinal center reaction.