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

Cell Reports
Victor GreiffSai T Reddy

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.

Citations

Feb 6, 2018·Annual Review of Immunology·Andrew J MacphersonStephanie C Ganal-Vonarburg
Sep 20, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Victor GreiffSai T Reddy
Dec 26, 2017·Frontiers in Immunology·Aleksandr KovaltsukJohannes Trück
Feb 28, 2018·Cell Biology and Toxicology·Xiao Liu, Jinghua Wu
Feb 19, 2020·PLoS Computational Biology·Aleksandr KovaltsukCharlotte M Deane
Sep 16, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aleksandr KovaltsukKonrad Krawczyk
May 16, 2020·The Journal of Biological Chemistry·Claire Marks, Charlotte M Deane
Oct 5, 2019·Scientific Reports·Nancy ChaayaSéverine Padiolleau-Lefèvre
Aug 15, 2018·Frontiers in Immunology·Oren AvramYariv Wine
May 6, 2020·Viral Immunology·Rhiannon R PenkertJulia L Hurwitz
Jun 18, 2020·Frontiers in Cellular and Infection Microbiology·Alexander YermanosSai T Reddy
Aug 28, 2020·Frontiers in Immunology·Marie GhraichyJohannes Trück
Dec 21, 2017·Immunogenetics·Andrew M Collins, Katherine J L Jackson
Oct 16, 2018·Frontiers in Immunology·Susana MagadanPierre Boudinot
May 5, 2018·Nature Protocols·Peter ChovanecAnne E Corcoran
Mar 23, 2019·Nature Communications·Enkelejda MihoSai T Reddy
Jun 18, 2020·Frontiers in Immunology·Alexander YermanosAnnette Oxenius
May 3, 2020·Communications Biology·Kannan SankarIsidro Hötzel
Mar 26, 2019·Nanotechnology·Yaron HillmanYariv Wine
Oct 20, 2018·Frontiers in Immunology·Alexander Dimitri YermanosSai T Reddy
Sep 10, 2020·IScience·Lucia CsepregiSai T Reddy
Oct 30, 2020·Nature·Carla R NowosadGabriel D Victora
Mar 2, 2021·PLoS Computational Biology·Matthew I J RaybouldCharlotte M Deane
Apr 23, 2021·NAR Genomics and Bioinformatics·Alexander YermanosSai T Reddy
Apr 15, 2021·Annual Review of Chemical and Biomolecular Engineering·Margarita PertsevaSai T Reddy
Jul 3, 2021·Frontiers in Immunology·Eriberto N NataliEnkelejda Miho

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