title: Defining antigen-specific plasmablast and memory B cell subsets in human blood after viral infection or vaccination.
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.
authors.affiliation: Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA.|Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Ellebedy
authors.affiliation: Department of Pathology, Stanford University, Stanford, California, USA.
authors.forename: Katherine J L
authors.initials: KJ
authors.lastname: Jackson
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA.|Department of Urology, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Haydn T
authors.initials: HT
authors.lastname: Kissick
authors.affiliation: Department of Pathology, School of Medicine, Emory University, Atlanta, Georgia, USA.|Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Helder I
authors.initials: HI
authors.lastname: Nakaya
authors.affiliation: Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA.|Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Carl W
authors.initials: CW
authors.lastname: Davis
authors.affiliation: Department of Pathology, Stanford University, Stanford, California, USA.
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Roskin
authors.affiliation: Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, USA.|Viral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Anita K
authors.initials: AK
authors.lastname: McElroy
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Oshansky
authors.affiliation: Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Rivka
authors.initials: R
authors.lastname: Elbein
authors.affiliation: Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Shine
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Lyon
authors.affiliation: Viral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
authors.affiliation: Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Aneesh K
authors.initials: AK
authors.lastname: Mehta
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.affiliation: Department of Pathology, Stanford University, Stanford, California, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boyd
authors.affiliation: Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA.|Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002999:Clone Cells; D029043:Ebolavirus / Q000502:physiology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D009980:Influenza A virus / Q000502:physiology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008213:Lymphocyte Activation; D051757:PAX5 Transcription Factor / Q000378:metabolism*; D010950:Plasma Cells / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D014611:Vaccination; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human