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Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children

Accurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important for understanding repertoire responses to infection and vaccination. We develop molecular identifier clustering-based immune repertoire sequencing (MIDCIRS) and use it to study age-r...

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Autores principales: Wendel, Ben S., He, Chenfeng, Qu, Mingjuan, Wu, Di, Hernandez, Stefany M., Ma, Ke-Yue, Liu, Eugene W., Xiao, Jun, Crompton, Peter D., Pierce, Susan K., Ren, Pengyu, Chen, Keke, Jiang, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599618/
https://www.ncbi.nlm.nih.gov/pubmed/28912592
http://dx.doi.org/10.1038/s41467-017-00645-x
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author Wendel, Ben S.
He, Chenfeng
Qu, Mingjuan
Wu, Di
Hernandez, Stefany M.
Ma, Ke-Yue
Liu, Eugene W.
Xiao, Jun
Crompton, Peter D.
Pierce, Susan K.
Ren, Pengyu
Chen, Keke
Jiang, Ning
author_facet Wendel, Ben S.
He, Chenfeng
Qu, Mingjuan
Wu, Di
Hernandez, Stefany M.
Ma, Ke-Yue
Liu, Eugene W.
Xiao, Jun
Crompton, Peter D.
Pierce, Susan K.
Ren, Pengyu
Chen, Keke
Jiang, Ning
author_sort Wendel, Ben S.
collection PubMed
description Accurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important for understanding repertoire responses to infection and vaccination. We develop molecular identifier clustering-based immune repertoire sequencing (MIDCIRS) and use it to study age-related antibody repertoire development and diversification before and during acute malaria in infants (< 12 months old) and toddlers (12–47 months old) with 4−8 ml of blood. Here, we show this accurate and high-coverage repertoire-sequencing method can use as few as 1000 naive B cells. Unexpectedly, we discover high levels of somatic hypermutation in infants as young as 3 months old. Antibody clonal lineage analysis reveals that somatic hypermutation levels are increased in both infants and toddlers upon infection, and memory B cells isolated from individuals who previously experienced malaria continue to induce somatic hypermutations upon malaria rechallenge. These results highlight the potential of antibody repertoire diversification in infants and toddlers.
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spelling pubmed-55996182017-09-18 Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children Wendel, Ben S. He, Chenfeng Qu, Mingjuan Wu, Di Hernandez, Stefany M. Ma, Ke-Yue Liu, Eugene W. Xiao, Jun Crompton, Peter D. Pierce, Susan K. Ren, Pengyu Chen, Keke Jiang, Ning Nat Commun Article Accurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important for understanding repertoire responses to infection and vaccination. We develop molecular identifier clustering-based immune repertoire sequencing (MIDCIRS) and use it to study age-related antibody repertoire development and diversification before and during acute malaria in infants (< 12 months old) and toddlers (12–47 months old) with 4−8 ml of blood. Here, we show this accurate and high-coverage repertoire-sequencing method can use as few as 1000 naive B cells. Unexpectedly, we discover high levels of somatic hypermutation in infants as young as 3 months old. Antibody clonal lineage analysis reveals that somatic hypermutation levels are increased in both infants and toddlers upon infection, and memory B cells isolated from individuals who previously experienced malaria continue to induce somatic hypermutations upon malaria rechallenge. These results highlight the potential of antibody repertoire diversification in infants and toddlers. Nature Publishing Group UK 2017-09-14 /pmc/articles/PMC5599618/ /pubmed/28912592 http://dx.doi.org/10.1038/s41467-017-00645-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wendel, Ben S.
He, Chenfeng
Qu, Mingjuan
Wu, Di
Hernandez, Stefany M.
Ma, Ke-Yue
Liu, Eugene W.
Xiao, Jun
Crompton, Peter D.
Pierce, Susan K.
Ren, Pengyu
Chen, Keke
Jiang, Ning
Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children
title Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children
title_full Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children
title_fullStr Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children
title_full_unstemmed Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children
title_short Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children
title_sort accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599618/
https://www.ncbi.nlm.nih.gov/pubmed/28912592
http://dx.doi.org/10.1038/s41467-017-00645-x
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