期刊
EBIOMEDICINE
卷 2, 期 12, 页码 2070-2079出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2015.11.034
关键词
Vaccination; Immunoglobulin repertoire; B cell repertoire; mAbs
资金
- MRC [G1000800, MC_UU_12010/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [1240827] Funding Source: researchfish
- Cancer Research UK [17722] Funding Source: researchfish
- Medical Research Council [MC_UU_12010/1, G1000800e, G1000800] Funding Source: researchfish
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. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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