title: Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements.
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.
authors: 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.
authors: Katherine J L
authors: KJ
authors: Jackson
authors: Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA.
authors: Yi
authors: Y
authors: Liu
authors: Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors: Krishna M
authors: KM
authors: Roskin
authors: Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors: Jacob
authors: J
authors: Glanville
authors: Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors: Ramona A
authors: RA
authors: Hoh
authors: Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors: Katie
authors: K
authors: Seo
authors: Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors: Eleanor L
authors: EL
authors: Marshall
authors: Duke Human Vaccine Institute, Durham, NC 27710, USA.
authors: Thaddeus C
authors: TC
authors: Gurley
authors: Duke Human Vaccine Institute, Durham, NC 27710, USA.
authors: M Anthony
authors: MA
authors: Moody
authors: Duke Human Vaccine Institute, Durham, NC 27710, USA.
authors: Barton F
authors: BF
authors: Haynes
authors: Duke Human Vaccine Institute, Durham, NC 27710, USA.
authors: Emmanuel B
authors: EB
authors: Walter
authors: Duke Human Vaccine Institute, Durham, NC 27710, USA.
authors: Hua-Xin
authors: HX
authors: Liao
authors: 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.
authors: Randy A
authors: RA
authors: Albrecht
authors: 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.
authors: Adolfo
authors: A
authors: García-Sastre
authors: Protein Engineering, Rinat-Pfizer Inc., South San Francisco, CA 94080, USA.
authors: Javier
authors: J
authors: Chaparro-Riggers
authors: Protein Engineering, Rinat-Pfizer Inc., South San Francisco, CA 94080, USA.
authors: Arvind
authors: A
authors: Rajpal
authors: Protein Engineering, Rinat-Pfizer Inc., South San Francisco, CA 94080, USA.
authors: Jaume
authors: J
authors: Pons
authors: 454 Life Sciences Corporation, a Roche Company, Branford, CT 06405, USA.
authors: Birgitte B
authors: BB
authors: Simen
authors: 454 Life Sciences Corporation, a Roche Company, Branford, CT 06405, USA.
authors: Bozena
authors: B
authors: Hanczaruk
authors: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
authors: Cornelia L
authors: CL
authors: Dekker
authors: Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
authors: Jonathan
authors: J
authors: Laserson
authors: Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
authors: Daphne
authors: D
authors: Koller
authors: Department of Microbiology and Immunology and Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute.
authors: Mark M
authors: MM
authors: Davis
authors: Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors: Andrew Z
authors: AZ
authors: Fire
authors: Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: sboyd1@stanford.edu.
authors: Scott D
authors: SD
authors: Boyd
mesh_terms: D000914:Antibodies, Viral / Q000235:genetics* / Q000276:immunology*; D000917:Antibody Formation; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines