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

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.

Schlagwörter

Systems immunology, Lg-seq, Bioinformatics

Fachgebiet (DDC)

600 - Technik, Medizin, angewandte Wissenschaften

Projekt

Veranstaltung

Startdatum der Ausstellung

Enddatum der Ausstellung

Startdatum der Konferenz

Enddatum der Konferenz

Datum der letzten Prüfung

ISBN

ISSN

2211-1247
2639-1856

Sprache

Englisch

Während FHNW Zugehörigkeit erstellt

Nein

Zukunftsfelder FHNW

Publikationsstatus

Veröffentlicht

Begutachtung

Peer-Review der ganzen Publikation

Open Access-Status

Gold

Lizenz

Zitation

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

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