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

  • Greiff V Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
  • Menzel U Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
  • Miho E Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
  • Weber C Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
  • Riedel R German Rheumatism Research Center, a Leibniz Institute, Berlin 10117, Germany.
  • Cook S Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
  • Valai A Shire, Research & Innovations, Research Immunology, Vienna 1221, Austria.
  • Lopes T Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
  • Radbruch A German Rheumatism Research Center, a Leibniz Institute, Berlin 10117, Germany.
  • Winkler TH Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, Department Biologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054, Germany.
  • Reddy ST Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland. Electronic address: sai.reddy@ethz.ch.
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  • 2017-05-18
Published in:
  • Cell reports. - 2017
Ig-seq
bioinformatics
systems immunology
Animals
Antibodies
Antigens
B-Lymphocytes
Cell Proliferation
Clone Cells
Germ Cells
Mice, Inbred C57BL
Plasma Cells
Systems Analysis
English 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.
Language
  • English
Open access status
gold
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Persistent URL
https://folia.unifr.ch/global/documents/143692
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