Systems analysis reveals high genetic and antigen-driven predetermination of antibody repertoires throughout B cell development

Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Cell Reports
Special issue
DOI of the original publication
Link
Series
Series number
Volume
19
Issue / Number
7
Pages / Duration
1467-1478
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Publisher / Publishing institution
Cell Press
Place of publication / Event location
Edition
Version
Programming language
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Practice partner / Client
Abstract
Antibody repertoire diversity and plasticity is crucial for broad protective immunity. Repertoires change in size and diversity across multiple B cell developmental stages and in response to antigen exposure. However, we still lack fundamental quantitative understanding of the extent to which repertoire diversity is predetermined. Therefore, we implemented a systems immunology framework for quantifying repertoire predetermination on three distinct levels: (1) B cell development (pre-B cell, naive B cell, plasma cell), (2) antigen exposure (three structurally different proteins), and (3) four antibody repertoire components (V-gene usage, clonal expansion, clonal diversity, repertoire size) extracted from antibody repertoire sequencing data (400 million reads). Across all three levels, we detected a dynamic balance of high genetic (e.g., >90% for V-gene usage and clonal expansion in naive B cells) and antigen-driven (e.g., 40% for clonal diversity in plasma cells) predetermination and stochastic variation. Our study has implications for the prediction and manipulation of humoral immunity.
Keywords
Systems immunology, Lg-seq, Bioinformatics
Project
Event
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ISBN
ISSN
2211-1247
2639-1856
Language
English
Created during FHNW affiliation
No
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Gold
License
'https://creativecommons.org/licenses/by-nc-nd/4.0/'
Citation
Greiff, V., Menzel, U., Miho, E., Weber, C., Riedel, R., Cook, S., Valai, A., Lopes, T., Radbruch, A., Winkler, T. H., & Reddy, S. T. (2017). Systems analysis reveals high genetic and antigen-driven predetermination of antibody repertoires throughout B cell development. Cell Reports, 19(7), 1467–1478. https://doi.org/10.1016/j.celrep.2017.04.054