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Spec-seq unveils transcriptional subpopulations of antibody-secreting cells following influenza vaccination
Karlynn E. Neu, … , Aly A. Khan, Patrick C. Wilson
Karlynn E. Neu, … , Aly A. Khan, Patrick C. Wilson
Published January 2, 2019; First published November 19, 2018
Citation Information: J Clin Invest. 2019;129(1):93-105. https://doi.org/10.1172/JCI121341.
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Categories: Research Article Immunology Vaccines

Spec-seq unveils transcriptional subpopulations of antibody-secreting cells following influenza vaccination

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Abstract

Vaccines are among the most effective public health tools for combating certain infectious diseases such as influenza. The role of the humoral immune system in vaccine-induced protection is widely appreciated; however, our understanding of how antibody specificities relate to B cell function remains limited due to the complexity of polyclonal antibody responses. To address this, we developed the Spec-seq framework, which allows for simultaneous monoclonal antibody (mAb) characterization and transcriptional profiling from the same single cell. Here, we present the first application of the Spec-seq framework, which we applied to human plasmablasts after influenza vaccination in order to characterize transcriptional differences governed by B cell receptor (BCR) isotype and vaccine reactivity. Our analysis did not find evidence of long-term transcriptional specialization between plasmablasts of different isotypes. However, we did find enhanced transcriptional similarity between clonally related B cells, as well as distinct transcriptional signatures ascribed by BCR vaccine recognition. These data suggest IgG and IgA vaccine–positive plasmablasts are largely similar, whereas IgA vaccine–negative cells appear to be transcriptionally distinct from conventional, terminally differentiated, antigen-induced peripheral blood plasmablasts.

Authors

Karlynn E. Neu, Jenna J. Guthmiller, Min Huang, Jennifer La, Marcos C. Vieira, Kangchon Kim, Nai-Ying Zheng, Mario Cortese, Micah E. Tepora, Natalie J. Hamel, Karla Thatcher Rojas, Carole Henry, Dustin Shaw, Charles L. Dulberger, Bali Pulendran, Sarah Cobey, Aly A. Khan, Patrick C. Wilson

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Figure 1

Experimental approach and characterization of influenza-induced plasmablast populations.

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Experimental approach and characterization of influenza-induced plasmabl...
(A) Experimental outline. (B) Sorting strategy. IgM– plasmablasts were identified as CD19+CD27++CD38++ and either IgG+ or IgA+. (C) Frequency of total plasmablasts of each isotype as detected during cell sorting and through anti-Ig ELISPOT. The ELISPOT data also report the frequency of vaccine-specific plasmablasts (QIV). Line indicates frequency mean. (D) Heatmap of all 291 single cells, clustered by their relative expression of the 4 IgG subtype genes and the 2 IgA subtype genes. Annotation bars across the top show the mAb vaccine binding and 3 levels of BCR isotype validation. (E) tSNE projection of the entire transcriptome of all 291 cells colored by group ID and with monoclonal antibody vaccine binding area under the curve (AUC) indicated by spot size.
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