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Cell Host Microbe. 2014 Jul 9;16(1):105-14. doi: 10.1016/j.chom.2014.05.013. Epub 2014 Jun 26.

Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements.

Author information

1
Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA; School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW 2052, Australia.
2
Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA.
3
Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
4
Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA.
5
Duke Human Vaccine Institute, Durham, NC 27710, USA.
6
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
7
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
8
Protein Engineering, Rinat-Pfizer Inc., South San Francisco, CA 94080, USA.
9
454 Life Sciences Corporation, a Roche Company, Branford, CT 06405, USA.
10
Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
11
Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
12
Department of Microbiology and Immunology and Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute.
13
Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA.
14
Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: sboyd1@stanford.edu.

Abstract

B cells produce a diverse antibody repertoire by undergoing gene rearrangements. Pathogen exposure induces the clonal expansion of B cells expressing antibodies that can bind the infectious agent. To assess human B cell responses to trivalent seasonal influenza and monovalent pandemic H1N1 vaccination, we sequenced gene rearrangements encoding the immunoglobulin heavy chain, a major determinant of epitope recognition. The magnitude of B cell clonal expansions correlates with an individual's secreted antibody response to the vaccine, and the expanded clones are enriched with those expressing influenza-specific monoclonal antibodies. Additionally, B cell responses to pandemic influenza H1N1 vaccination and infection in different people show a prominent family of convergent antibody heavy chain gene rearrangements specific to influenza antigens. These results indicate that microbes can induce specific signatures of immunoglobulin gene rearrangements and that pathogen exposure can potentially be assessed from B cell repertoires.

PMID:
24981332
PMCID:
PMC4158033
DOI:
10.1016/j.chom.2014.05.013
[Indexed for MEDLINE]
Free PMC Article

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