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 naïve B cells or memory B cells in the context of a germinal center reaction.
Keywords: plasmablasts, viral infection, antibodies, single cell RNAseq, dengue, B cell memory, antibody-secreting cells
Rouers, Angeline and Appanna, Ramapraba and Chevrier, Marion and Lum, Josephine and Lau, MaiChan and Tan, Lingqiao and Tay, Alicia and Sathiakumar, Durgalakshmi and Kaur, Kaval and Boehme, Julia and Leo, Yee-Sin and Howland, Shanshan W. and Singhal, Amit and Chen, Jinmiao and Fink, Katja, CD27
hi Plasmablasts are Activated B Cells of Mixed Origin with Distinct Function. Available at SSRN: https://ssrn.com/abstract=3631403 or http://dx.doi.org/10.2139/ssrn.3631403
This version of the paper has not been formally peer reviewed.