Systems analysis reveals high genetic and antigen-driven predetermination of antibody repertoires throughout B cell development
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Author (Corporation)
Publication date
16.05.2017
Typ of student thesis
Course of study
Type
01A - Journal article
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Editor (Corporation)
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Parent work
Cell Reports
Special issue
DOI of the original publication
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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
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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
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ISBN
ISSN
2211-1247
2639-1856
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
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