Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences

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 ch...

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Main Authors: Galson, J, Trück, J, Fowler, A, Clutterbuck, E, Münz, M, Cerundolo, V, Reinhard, C, van der Most, R, Pollard, A, Lunter, G, Kelly, D
Format: Journal article
Language:English
Published: Elsevier 2015
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author Galson, J
Trück, J
Fowler, A
Clutterbuck, E
Münz, M
Cerundolo, V
Reinhard, C
van der Most, R
Pollard, A
Lunter, G
Kelly, D
author_facet Galson, J
Trück, J
Fowler, A
Clutterbuck, E
Münz, M
Cerundolo, V
Reinhard, C
van der Most, R
Pollard, A
Lunter, G
Kelly, D
author_sort Galson, J
collection OXFORD
description 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.
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spelling oxford-uuid:9cedb41f-4ec3-459e-92d3-a2524ed8f3482022-03-27T00:39:36ZAnalysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequencesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9cedb41f-4ec3-459e-92d3-a2524ed8f348EnglishSymplectic Elements at OxfordElsevier2015Galson, JTrück, JFowler, AClutterbuck, EMünz, MCerundolo, VReinhard, Cvan der Most, RPollard, ALunter, GKelly, DGenerating 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.
spellingShingle Galson, J
Trück, J
Fowler, A
Clutterbuck, E
Münz, M
Cerundolo, V
Reinhard, C
van der Most, R
Pollard, A
Lunter, G
Kelly, D
Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences
title Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences
title_full Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences
title_fullStr Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences
title_full_unstemmed Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences
title_short Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences
title_sort analysis of b cell repertoire dynamics following hepatitis b vaccination in humans and enrichment of vaccine specific antibody sequences
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