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EBioMedicine. 2015 Nov 24;2(12):2070-9. doi: 10.1016/j.ebiom.2015.11.034. eCollection 2015 Dec.

Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences.

Author information

1
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford OX3 7LE, United Kingdom; Welcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
2
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford OX3 7LE, United Kingdom; Paediatric Immunology, University Children's Hospital, Zürich, 8032, Switzerland.
3
Welcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
4
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford OX3 7LE, United Kingdom.
5
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS, United Kingdom.
6
Miltenyi Biotec, Bergisch Gladbach, Germany.
7
GSK Vaccines, Rixensart, Belgium.

Abstract

Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.

KEYWORDS:

B cell repertoire; Immunoglobulin repertoire; Vaccination; mAbs

PMID:
26844287
PMCID:
PMC4703725
DOI:
10.1016/j.ebiom.2015.11.034
[Indexed for MEDLINE]
Free PMC Article

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