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

Clinically 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 CD27(high) CD38(high) plasmablasts 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.

Automated summary

This study found that CD27(high) CD38(high) plasmablasts from patients with primary or secondary dengue virus infection can be divided into three transcriptionally and functionally distinct clusters. The largest cluster is related to plasma cells and codes for IgG1 isotype serotype cross-reactive antibodies, while the other two clusters show low levels of antibody gene expression but are associated with oxidative phosphorylation, EIF2 pathway, and mitochondrial dysfunction.