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

Angeline Rouers; Ramapraba Appanna; Marion Chevrier; Josephine Lum; Mai Chan Lau; Lingqiao Tan; Thomas Loy; Alicia Tay; Raman Sethi; Durgalakshmi Sathiakumar; Kaval Kaur; Julia Böhme; Yee-Sin Leo; Laurent Renia; Shanshan W Howland; Amit Singhal; Jinmiao Chen; Katja Fink

doi:10.1016/j.isci.2021.102482

CD27^hiCD38^hi plasmablasts are activated B cells of mixed origin with distinct function

iScience. 2021 Apr 29;24(5):102482. doi: 10.1016/j.isci.2021.102482. eCollection 2021 May 21.

Authors

Angeline Rouers^{1

2}, Ramapraba Appanna¹, Marion Chevrier¹, Josephine Lum¹, Mai Chan Lau¹, Lingqiao Tan¹, Thomas Loy^{1

2}, Alicia Tay¹, Raman Sethi¹, Durgalakshmi Sathiakumar¹, Kaval Kaur¹, Julia Böhme¹, Yee-Sin Leo^{3

4

5

6

7

8}, Laurent Renia^{1

2}, Shanshan W Howland¹, Amit Singhal^{1

2}, Jinmiao Chen¹, Katja Fink¹

Affiliations

¹ Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
² A∗STAR ID Labs, Agency for Science, Technology and Research, Singapore 138648, Singapore.
³ National Centre for Infectious Diseases, Singapore 308442, Singapore.
⁴ School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
⁵ Lee Kong Chian School of Medicine, Singapore 308232, Singapore.
⁶ Tan Tock Seng Hospital, Singapore 308433, Singapore.
⁷ Yong Loo Lin School of Medicine, Singapore 119228, Singapore.
⁸ Saw Swee Hock School of Public Health, Singapore 117549, Singapore.

Abstract

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^highCD38^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.

Keywords: Cell biology; Functional aspects of cell biology; Immunology; Systems biology.