Defining antigen-specific plasmablast and memory B cell subsets in human blood after viral infection or vaccination

• Type of Material: Article
• Authors: Ali Ellebedy, Emory University; Katherine J.L. Jackson, Stanford University; Haydn Kissick, Emory University; Helder I. Nakaya, Emory University; Carl W. Davis, Emory University; Krishna M. Roskin, Stanford University; Anita K. McElroy, Emory University; Christine M. Oshansky, St Jude Childrens Research Hospital; Rivka Elbein, Emory University; Shine Thomas, Emory University; George Lyon III, Emory University; Christina F. Spiropoulou, US Centers for Disease Control and Prevention; Aneesh Mehta, Emory University; Paul G. Thomas, St Jude Childrens Research Hospital; Scott D. Boyd, Stanford University; Rafi Ahmed, Emory University
• Language: English
• Date: 2016-10-01
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Nature America, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/ni.3533
• Title of Journal or Parent Work: Nature Immunology
• ISSN: 1529-2908
• Volume: 17
• Issue: 10
• Start Page: 1226
• End Page: 1234
• Grant/Funding Information: This work was funded in parts by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) contract number HHSN266200700006C, grants 1P01AI097092, U19AI117891 and Advanced Immunization Technologies (ADITEC) #280873, European Union (to R.A.), and by grants U19AI09525801, UM1AI100663, and U01AI104342 (to S.D.B.). A.E. is supported by the training grant (T32AI074492) from the National Institute of Allergy and Infectious Diseases. H.I.N. receives investigator fellowship from CNPq, Brazil.
• Keywords: GENERATION; INFLUENZA INFECTION; ANTIBODIES; VIRUS-INFECTION; Life Sciences & Biomedicine; COMMITMENT; Immunology; NETWORKS; Science & Technology; IMMUNE-RESPONSES
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology

Abstract

Antigen-specific B cells bifurcate into antibody-secreting cells (ASCs) and memory B cells (MBCs) after infection or vaccination. ASCs (plasmablasts) have been extensively studied in humans, but less is known about B cells that become activated but do not differentiate into plasmablasts. Here we have defined the phenotype and transcriptional program of a subset of antigen-specific B cells, which we have called 'activated B cells' (ABCs), that were distinct from ASCs and were committed to the MBC lineage. We detected ABCs in humans after infection with Ebola virus or influenza virus and also after vaccination. By simultaneously analyzing antigen-specific ASCs and ABCs in human blood after vaccination against influenza virus, we investigated the clonal overlap and extent of somatic hypermutation (SHM) in the ASC (effector) and ABC (memory) lineages. Longitudinal tracking of vaccination-induced hemagglutinin (HA)-specific clones revealed no overall increase in SHM over time, which suggested that repeated annual immunization might have limitations in enhancing the quality of influenza-virus-specific antibody.