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Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics

The immune system produces a diverse repertoire of immunoglobulins in response to foreign antigens. During B-cell development, VDJ recombination and somatic mutations generate diversity, whereas selection processes remove it. Using both proteomic and NGS approaches, we characterized the immune reper...

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Autores principales: VanDuijn, Martijn M., Dekker, Lennard J., van IJcken, Wilfred F. J., Sillevis Smitt, Peter A. E., Luider, Theo M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650670/
https://www.ncbi.nlm.nih.gov/pubmed/29085363
http://dx.doi.org/10.3389/fimmu.2017.01286
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author VanDuijn, Martijn M.
Dekker, Lennard J.
van IJcken, Wilfred F. J.
Sillevis Smitt, Peter A. E.
Luider, Theo M.
author_facet VanDuijn, Martijn M.
Dekker, Lennard J.
van IJcken, Wilfred F. J.
Sillevis Smitt, Peter A. E.
Luider, Theo M.
author_sort VanDuijn, Martijn M.
collection PubMed
description The immune system produces a diverse repertoire of immunoglobulins in response to foreign antigens. During B-cell development, VDJ recombination and somatic mutations generate diversity, whereas selection processes remove it. Using both proteomic and NGS approaches, we characterized the immune repertoires in groups of rats after immunization with purified antigens. Proteomics and NGS data on the repertoire are in qualitative agreement, but did show quantitative differences that may relate to differences between the biological niches that were sampled for these approaches. Both methods contributed complementary information in the characterization of the immune repertoire. It was found that the immune repertoires resulting from each antigen had many similarities that allowed samples to cluster together, and that mutated immunoglobulin peptides were shared among animals with a response to the same antigen significantly more than for different antigens. However, the number of shared sequences decreased in a log-linear fashion relative to the number of animals that share them, which may affect future applications. A phylogenetic analysis on the NGS reads showed that reads from different individuals immunized with the same antigen populated distinct branches of the phylogram, an indication that the repertoire had converged. Also, similar mutation patterns were found in branches of the phylogenetic tree that were associated with antigen-specific immunoglobulins through proteomics data. Thus, data from different analysis methods and different experimental platforms show that the immunoglobulin repertoires of immunized animals have overlapping and converging features. With additional research, this may enable interesting applications in biotechnology and clinical diagnostics.
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spelling pubmed-56506702017-10-30 Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics VanDuijn, Martijn M. Dekker, Lennard J. van IJcken, Wilfred F. J. Sillevis Smitt, Peter A. E. Luider, Theo M. Front Immunol Immunology The immune system produces a diverse repertoire of immunoglobulins in response to foreign antigens. During B-cell development, VDJ recombination and somatic mutations generate diversity, whereas selection processes remove it. Using both proteomic and NGS approaches, we characterized the immune repertoires in groups of rats after immunization with purified antigens. Proteomics and NGS data on the repertoire are in qualitative agreement, but did show quantitative differences that may relate to differences between the biological niches that were sampled for these approaches. Both methods contributed complementary information in the characterization of the immune repertoire. It was found that the immune repertoires resulting from each antigen had many similarities that allowed samples to cluster together, and that mutated immunoglobulin peptides were shared among animals with a response to the same antigen significantly more than for different antigens. However, the number of shared sequences decreased in a log-linear fashion relative to the number of animals that share them, which may affect future applications. A phylogenetic analysis on the NGS reads showed that reads from different individuals immunized with the same antigen populated distinct branches of the phylogram, an indication that the repertoire had converged. Also, similar mutation patterns were found in branches of the phylogenetic tree that were associated with antigen-specific immunoglobulins through proteomics data. Thus, data from different analysis methods and different experimental platforms show that the immunoglobulin repertoires of immunized animals have overlapping and converging features. With additional research, this may enable interesting applications in biotechnology and clinical diagnostics. Frontiers Media S.A. 2017-10-16 /pmc/articles/PMC5650670/ /pubmed/29085363 http://dx.doi.org/10.3389/fimmu.2017.01286 Text en Copyright © 2017 VanDuijn, Dekker, van IJcken, Sillevis Smitt and Luider. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
VanDuijn, Martijn M.
Dekker, Lennard J.
van IJcken, Wilfred F. J.
Sillevis Smitt, Peter A. E.
Luider, Theo M.
Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics
title Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics
title_full Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics
title_fullStr Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics
title_full_unstemmed Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics
title_short Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics
title_sort immune repertoire after immunization as seen by next-generation sequencing and proteomics
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650670/
https://www.ncbi.nlm.nih.gov/pubmed/29085363
http://dx.doi.org/10.3389/fimmu.2017.01286
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