CD27CD38 Plasmablasts Are Activated B Cells of Mixed Origin with Distinct Function

Overview

Journal iScience

Publisher Cell Press

Date 2021 Jun 11

PMID 34113823

Citations 9

Authors

Angeline Rouers

Ramapraba Appanna

Marion Chevrier

Josephine Lum

Mai Chan Lau

Lingqiao Tan

Thomas Loy

Alicia Tay

Raman Sethi

Durgalakshmi Sathiakumar

Kaval Kaur

Julia Bohme

Yee-Sin Leo

Laurent Renia

Shanshan W Howland

Amit Singhal

Jinmiao Chen

Katja Fink

Affiliations

Soon will be listed here.

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 CD27CD38 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.

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References

Wrammert J, Onlamoon N, Akondy R, Perng G, Polsrila K, Chandele A . Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans. J Virol. 2012; 86(6):2911-8. PMC: 3302324. DOI: 10.1128/JVI.06075-11. View

Arpin C, Banchereau J, Liu Y . Memory B cells are biased towards terminal differentiation: a strategy that may prevent repertoire freezing. J Exp Med. 1997; 186(6):931-40. PMC: 2199043. DOI: 10.1084/jem.186.6.931. View

Rouvinski A, Guardado-Calvo P, Barba-Spaeth G, Duquerroy S, Vaney M, Kikuti C . Recognition determinants of broadly neutralizing human antibodies against dengue viruses. Nature. 2015; 520(7545):109-13. DOI: 10.1038/nature14130. View

Carter M, Mitchell R, Meyer Sauteur P, Kelly D, Truck J . The Antibody-Secreting Cell Response to Infection: Kinetics and Clinical Applications. Front Immunol. 2017; 8:630. PMC: 5451496. DOI: 10.3389/fimmu.2017.00630. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Shugay M, Bagaev D, Turchaninova M, Bolotin D, Britanova O, Putintseva E . VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires. PLoS Comput Biol. 2015; 11(11):e1004503. PMC: 4659587. DOI: 10.1371/journal.pcbi.1004503. View

Benckert J, Schmolka N, Kreschel C, Zoller M, Sturm A, Wiedenmann B . The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific. J Clin Invest. 2011; 121(5):1946-55. PMC: 3083800. DOI: 10.1172/JCI44447. View

Basso K, Klein U, Niu H, Stolovitzky G, Tu Y, Califano A . Tracking CD40 signaling during germinal center development. Blood. 2004; 104(13):4088-96. DOI: 10.1182/blood-2003-12-4291. View

Tas J, Mesin L, Pasqual G, Targ S, Jacobsen J, Mano Y . Visualizing antibody affinity maturation in germinal centers. Science. 2016; 351(6277):1048-54. PMC: 4938154. DOI: 10.1126/science.aad3439. View

10.

Durham N, Agrawal A, Waltari E, Croote D, Zanini F, Fouch M . Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics. Elife. 2019; 8. PMC: 6927745. DOI: 10.7554/eLife.52384. View

11.

Picelli S, Faridani O, Bjorklund A, Winberg G, Sagasser S, Sandberg R . Full-length RNA-seq from single cells using Smart-seq2. Nat Protoc. 2014; 9(1):171-81. DOI: 10.1038/nprot.2014.006. View

12.

Fibriansah G, Tan J, Smith S, de Alwis A, Ng T, Kostyuchenko V . A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface. EMBO Mol Med. 2014; 6(3):358-71. PMC: 3958310. DOI: 10.1002/emmm.201303404. View

13.

Lai C, Williams K, Wu Y, Knight S, Balmaseda A, Harris E . Analysis of cross-reactive antibodies recognizing the fusion loop of envelope protein and correlation with neutralizing antibody titers in Nicaraguan dengue cases. PLoS Negl Trop Dis. 2013; 7(9):e2451. PMC: 3777924. DOI: 10.1371/journal.pntd.0002451. View

14.

Spencer J, Sollid L . The human intestinal B-cell response. Mucosal Immunol. 2016; 9(5):1113-24. DOI: 10.1038/mi.2016.59. View

15.

Stamper C, Wilson P . What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Is Affinity Maturation a Self-Defeating Process for Eliciting Broad Protection?. Cold Spring Harb Perspect Biol. 2017; 10(5). PMC: 5899041. DOI: 10.1101/cshperspect.a028803. View

16.

Angelo M, Grifoni A, ORourke P, Sidney J, Paul S, Peters B . Human CD4 T Cell Responses to an Attenuated Tetravalent Dengue Vaccine Parallel Those Induced by Natural Infection in Magnitude, HLA Restriction, and Antigen Specificity. J Virol. 2016; 91(5). PMC: 5309943. DOI: 10.1128/JVI.02147-16. View

17.

Xu M, Hadinoto V, Appanna R, Joensson K, Toh Y, Balakrishnan T . Plasmablasts generated during repeated dengue infection are virus glycoprotein-specific and bind to multiple virus serotypes. J Immunol. 2012; 189(12):5877-85. DOI: 10.4049/jimmunol.1201688. View

18.

Iversen R, Snir O, Stensland M, Kroll J, Steinsbo O, Korponay-Szabo I . Strong Clonal Relatedness between Serum and Gut IgA despite Different Plasma Cell Origins. Cell Rep. 2017; 20(10):2357-2367. PMC: 5603730. DOI: 10.1016/j.celrep.2017.08.036. View

19.

Isenberg J, Ridnour L, Dimitry J, Frazier W, Wink D, Roberts D . CD47 is necessary for inhibition of nitric oxide-stimulated vascular cell responses by thrombospondin-1. J Biol Chem. 2006; 281(36):26069-80. DOI: 10.1074/jbc.M605040200. View

20.

Kallies A, Hasbold J, Fairfax K, Pridans C, Emslie D, McKenzie B . Initiation of plasma-cell differentiation is independent of the transcription factor Blimp-1. Immunity. 2007; 26(5):555-66. DOI: 10.1016/j.immuni.2007.04.007. View