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Cell Rep. 2017 May 16;19(7):1467-1478. doi: 10.1016/j.celrep.2017.04.054.

Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development.

Author information

1
Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
2
German Rheumatism Research Center, a Leibniz Institute, Berlin 10117, Germany.
3
Shire, Research & Innovations, Research Immunology, Vienna 1221, Austria.
4
Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, Department Biologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054, Germany.
5
Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland. Electronic address: sai.reddy@ethz.ch.

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:

Ig-seq; bioinformatics; systems immunology

PMID:
28514665
DOI:
10.1016/j.celrep.2017.04.054
[Indexed for MEDLINE]
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