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

Greiff, V., Menzel, U., Miho, E., Weber, C., Riedel, re, R., Cook, S., et al. (2017). Systems analysis reveals high genetic and antigen-driven predetermination of antibody repertoires throughout B Cell development. Cell Reports, 19(7), 1467-1478. doi:10.1016/j.celrep.2017.04.054.

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 Creators:
Greiff, Victor1, Author
Menzel, Ulrike, Author
Miho, Enkelejda, Author
Weber, Cédric, Author
Riedel, re, René, Author
Cook, Skylar, Author
Valai, Atijeh, Author
Lopes, Telma, Author
Radbruch, Andreas, Author
Winkler, Thomas H., Author
Reddy, Sai T., Author
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1External Organizations, ou_persistent22              

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Free keywords: systems immunology; Ig-seq; bioinformatics
 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.

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Language(s): eng - English
 Dates: 2017-03-212016-07-072017-04-192017-05-162017
 Publication Status: Issued
 Pages: -
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 Identifiers: DOI: 10.1016/j.celrep.2017.04.054
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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 19 (7) Sequence Number: - Start / End Page: 1467 - 1478 Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247