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

Nature Immunology volume 17, pages 12261234 (2016) | Download Citation


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.

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We thank R. Karaffa and S. Durham for technical assistance. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (HHSN266200700006C, 1P01AI097092 and U19AI117891 to R.A.; T32AI074492 to A.E.; and U19AI09525801, UM1AI100663 and U01AI104342 to S.D.B.), Advanced Immunization Technologies (280873), the European Union (R.A.), the National Center for Advancing Translational Sciences (UL1TR000454 to A.K.M.) and The National Council for Scientific and Technological Development of Brazil (H.I.N.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health or that of the Centers for Disease Control and Prevention.

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Author notes

    • Ali H Ellebedy
    • , Katherine J L Jackson
    • , Scott D Boyd
    •  & Rafi Ahmed

    These authors contributed equally to this work.


  1. Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA.

    • Ali H Ellebedy
    • , Carl W Davis
    •  & Rafi Ahmed
  2. Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA.

    • Ali H Ellebedy
    • , Haydn T Kissick
    • , Carl W Davis
    •  & Rafi Ahmed
  3. Department of Pathology, Stanford University, Stanford, California, USA.

    • Katherine J L Jackson
    • , Krishna M Roskin
    •  & Scott D Boyd
  4. Department of Urology, School of Medicine, Emory University, Atlanta, Georgia, USA.

    • Haydn T Kissick
  5. Department of Pathology, School of Medicine, Emory University, Atlanta, Georgia, USA.

    • Helder I Nakaya
  6. Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.

    • Helder I Nakaya
  7. Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, USA.

    • Anita K McElroy
  8. Viral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

    • Anita K McElroy
    •  & Christina F Spiropoulou
  9. Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

    • Christine M Oshansky
    •  & Paul G Thomas
  10. Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia, USA.

    • Rivka Elbein
    • , Shine Thomas
    • , George M Lyon
    •  & Aneesh K Mehta


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A.H.E., K.J.L.J., S.D.B. and R.A. designed the study, interpreted data and wrote the paper; A.H.E. performed most of the experiments; K.J.L.J. performed next-generation sequencing of the IGH repertoire and devised, undertook and interpreted repertoire-data analysis; H.T.K. and H.I.N. analyzed the microarray data; C.W.D. and A.K.M. helped in data analysis and interpretation; K.M.R. processed repertoire-sequence data; and C.M.O., R.E., S.T., G.M.L., C.F.S., A.K.M. and P.G.T. helped in collecting and processing the clinical samples.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Scott D Boyd or Rafi Ahmed.

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    Supplementary Table 1

    192 genes that were differentially upregulated in the ABC subset

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