BCR repertoire sequencing: different patterns of B‐cell activation after two Meningococcal vaccines
Next‐generation sequencing was used to investigate the B‐cell receptor heavy chain transcript repertoire of different B‐cell subsets (naive, marginal zone (MZ), immunoglobulin M (IgM) memory and IgG memory) at baseline, and of plasma cells (PCs) 7 days following administration of serogroup ACWY meni...
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Published in | Immunology and cell biology Vol. 93; no. 10; pp. 885 - 895 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
Nature Publishing Group
01.11.2015
Blackwell Science Ltd |
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Abstract | Next‐generation sequencing was used to investigate the B‐cell receptor heavy chain transcript repertoire of different B‐cell subsets (naive, marginal zone (MZ), immunoglobulin M (IgM) memory and IgG memory) at baseline, and of plasma cells (PCs) 7 days following administration of serogroup ACWY meningococcal polysaccharide and protein–polysaccharide conjugate vaccines. Baseline B‐cell subsets could be distinguished from each other using a small number of repertoire properties (clonality, mutation from germline and complementarity‐determining region 3 (CDR3) length) that were conserved between individuals. However, analyzing the CDR3 amino‐acid sequence (which is particularly important for antigen binding) of the baseline subsets showed few sequences shared between individuals. In contrast, day 7 PCs demonstrated nearly 10‐fold greater sequence sharing between individuals than the baseline subsets, consistent with the PCs being induced by the vaccine antigen and sharing specificity for a more limited range of epitopes. By annotating PC sequences based on IgG subclass usage and mutation, and also comparing them with the sequences of the baseline cell subsets, we were able to identify different signatures after the polysaccharide and conjugate vaccines. PCs produced after conjugate vaccination were predominantly IgG1, and most related to IgG memory cells. In contrast, after polysaccharide vaccination, the PCs were predominantly IgG2, less mutated and were equally likely to be related to MZ, IgM memory or IgG memory cells. High‐throughput B‐cell repertoire sequencing thus provides a unique insight into patterns of B‐cell activation not possible from more conventional measures of immunogenicity. |
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AbstractList | Next-generation sequencing was used to investigate the B-cell receptor heavy chain transcript repertoire of different B-cell subsets (naive, marginal zone (MZ), immunoglobulin M (IgM) memory and IgG memory) at baseline, and of plasma cells (PCs) 7 days following administration of serogroup ACWY meningococcal polysaccharide and protein-polysaccharide conjugate vaccines. Baseline B-cell subsets could be distinguished from each other using a small number of repertoire properties (clonality, mutation from germline and complementarity-determining region 3 (CDR3) length) that were conserved between individuals. However, analyzing the CDR3 amino-acid sequence (which is particularly important for antigen binding) of the baseline subsets showed few sequences shared between individuals. In contrast, day 7 PCs demonstrated nearly 10-fold greater sequence sharing between individuals than the baseline subsets, consistent with the PCs being induced by the vaccine antigen and sharing specificity for a more limited range of epitopes. By annotating PC sequences based on IgG subclass usage and mutation, and also comparing them with the sequences of the baseline cell subsets, we were able to identify different signatures after the polysaccharide and conjugate vaccines. PCs produced after conjugate vaccination were predominantly IgG1, and most related to IgG memory cells. In contrast, after polysaccharide vaccination, the PCs were predominantly IgG2, less mutated and were equally likely to be related to MZ, IgM memory or IgG memory cells. High-throughput B-cell repertoire sequencing thus provides a unique insight into patterns of B-cell activation not possible from more conventional measures of immunogenicity. Next-generation sequencing was used to investigate the B cell receptor heavy chain transcript repertoire of different B cell subsets (naïve, marginal zone, IgM memory and IgG memory) at baseline, and of plasma cells 7 days following administration of serogroup ACWY meningococcal polysaccharide and protein-polysaccharide conjugate vaccines. Baseline B cell subsets could be distinguished from each other using a small number of repertoire properties (clonality, mutation from germ-line and complementarity-determining region 3 length) that were conserved between individuals. However, analyzing the complementarity-determining region 3 amino acid sequence (which is particularly important for antigen binding) of the baseline subsets showed few sequences shared between individuals. In contrast, day 7 plasma cells demonstrated nearly tenfold greater sequence sharing between individuals than the baseline subsets, consistent with the plasma cells being induced by the vaccine antigen, and sharing specificity for a more limited range of epitopes. By annotating plasma cell sequences based on IgG subclass usage and mutation, and also comparing them to the sequences of the baseline cell subsets, we were able to identify different signatures after the polysaccharide and conjugate vaccines. Plasma cells produced after conjugate vaccination were predominantly IgG1, and most related to IgG memory cells. In contrast, after polysaccharide vaccination, the plasma cells were predominantly IgG2, less mutated, and were equally likely to be related to marginal zone, IgM memory or IgG memory cells. High-throughput B cell repertoire sequencing thus provides a unique insight into patterns of B cell activation not possible from more conventional measures of immunogenicity. |
Author | Pollard, Andrew J Cerundolo, Vincenzo Clutterbuck, Elizabeth A Lunter, Gerton Münz, Márton Trück, Johannes Ramasamy, Maheshi N Kelly, Dominic F Fowler, Anna Galson, Jacob D |
AuthorAffiliation | 1 Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, OX3 7LE, United Kingdom 3 Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, United Kingdom 2 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom |
AuthorAffiliation_xml | – name: 1 Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, OX3 7LE, United Kingdom – name: 2 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom – name: 3 Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, United Kingdom |
Author_xml | – sequence: 1 givenname: Jacob D surname: Galson fullname: Galson, Jacob D email: jacob.galson@paediatrics.ox.ac.uk organization: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center – sequence: 2 givenname: Elizabeth A surname: Clutterbuck fullname: Clutterbuck, Elizabeth A organization: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center – sequence: 3 givenname: Johannes surname: Trück fullname: Trück, Johannes organization: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center – sequence: 4 givenname: Maheshi N surname: Ramasamy fullname: Ramasamy, Maheshi N organization: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center – sequence: 5 givenname: Márton surname: Münz fullname: Münz, Márton organization: Wellcome Trust Centre for Human Genetics, University of Oxford – sequence: 6 givenname: Anna surname: Fowler fullname: Fowler, Anna organization: Wellcome Trust Centre for Human Genetics, University of Oxford – sequence: 7 givenname: Vincenzo surname: Cerundolo fullname: Cerundolo, Vincenzo organization: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine – sequence: 8 givenname: Andrew J surname: Pollard fullname: Pollard, Andrew J organization: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center – sequence: 9 givenname: Gerton surname: Lunter fullname: Lunter, Gerton organization: Wellcome Trust Centre for Human Genetics, University of Oxford – sequence: 10 givenname: Dominic F surname: Kelly fullname: Kelly, Dominic F organization: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center |
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Snippet | Next‐generation sequencing was used to investigate the B‐cell receptor heavy chain transcript repertoire of different B‐cell subsets (naive, marginal zone... Next-generation sequencing was used to investigate the B-cell receptor heavy chain transcript repertoire of different B-cell subsets (naive, marginal zone... Next-generation sequencing was used to investigate the B cell receptor heavy chain transcript repertoire of different B cell subsets (naïve, marginal zone, IgM... |
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SubjectTerms | B-Lymphocyte Subsets - immunology B-Lymphocytes - immunology Complementarity Determining Regions - genetics Epitopes Epitopes, B-Lymphocyte - metabolism Genetic Variation - genetics High-Throughput Nucleotide Sequencing HLA-DR Antigens - metabolism Immunoglobulin G - metabolism Immunologic Memory - genetics Lymphocyte Activation - genetics Meningococcal Vaccines - administration & dosage Meningococcal Vaccines - immunology Principal Component Analysis Receptors, Antigen, B-Cell - genetics Transcriptome |
Title | BCR repertoire sequencing: different patterns of B‐cell activation after two Meningococcal vaccines |
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