Format

Send to

Choose Destination
Clin Immunol. 2014 Mar;151(1):55-65. doi: 10.1016/j.clim.2013.12.008. Epub 2014 Jan 9.

High-throughput sequencing of natively paired antibody chains provides evidence for original antigenic sin shaping the antibody response to influenza vaccination.

Author information

1
Division of Immunology and Rheumatology, Stanford University, CCSR 4135, 269 Campus Dr, Stanford, CA 94305, USA; VA Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, CA 94304, USA; Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
2
Division of Immunology and Rheumatology, Stanford University, CCSR 4135, 269 Campus Dr, Stanford, CA 94305, USA; VA Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, CA 94304, USA.
3
Division of Immunology and Rheumatology, Stanford University, CCSR 4135, 269 Campus Dr, Stanford, CA 94305, USA.
4
Division of Immunology and Rheumatology, Stanford University, CCSR 4135, 269 Campus Dr, Stanford, CA 94305, USA; VA Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, CA 94304, USA; Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: wrobins@stanford.edu.

Abstract

We developed a DNA barcoding method to enable high-throughput sequencing of the cognate heavy- and light-chain pairs of the antibodies expressed by individual B cells. We used this approach to elucidate the plasmablast antibody response to influenza vaccination. We show that >75% of the rationally selected plasmablast antibodies bind and neutralize influenza, and that antibodies from clonal families, defined by sharing both heavy-chain VJ and light-chain VJ sequence usage, do so most effectively. Vaccine-induced heavy-chain VJ regions contained on average >20 nucleotide mutations as compared to their predicted germline gene sequences, and some vaccine-induced antibodies exhibited higher binding affinities for hemagglutinins derived from prior years' seasonal influenza as compared to their affinities for the immunization strains. Our results show that influenza vaccination induces the recall of memory B cells that express antibodies that previously underwent affinity maturation against prior years' seasonal influenza, suggesting that 'original antigenic sin' shapes the antibody response to influenza vaccination.

KEYWORDS:

Antibody;; B cell; Influenza;

PMID:
24525048
PMCID:
PMC4006370
DOI:
10.1016/j.clim.2013.12.008
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center