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

• Published in: The Journal of clinical investigation Vol. 129; no. 1; pp. 93 - 105
• Main Authors: Neu, Karlynn E, Guthmiller, Jenna J, Huang, Min, La, Jennifer, Vieira, Marcos C, Kim, Kangchon, Zheng, Nai-Ying, Cortese, Mario, Tepora, Micah E, Hamel, Natalie J, Rojas, Karla Thatcher, Henry, Carole, Shaw, Dustin, Dulberger, Charles L, Pulendran, Bali, Cobey, Sarah, Khan, Aly A, Wilson, Patrick C
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.01.2019
• Subjects: Antibodies, Viral - immunology; Antigens; B-cell receptor; Bioinformatics; Biomedical research; Blood plasma; Data processing; Female; Humans; Immune system; Immunoglobulin A; Immunoglobulin A - immunology; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulins; Infections; Infectious diseases; Influenza; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Isotypes; Lymphocytes B; Male; Monoclonal antibodies; Peripheral blood; Plasma Cells - cytology; Plasma Cells - immunology; Prevention; Public health; Receptors, Antigen, B-Cell - immunology; Specialization; Transcription; Transcription, Genetic - drug effects; Transcription, Genetic - immunology; Vaccination; Vaccines; Adaptive immunity; Immunology; B cells; Vaccines; Influenza
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI121341

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.