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, Victor, Ulrike MENZEL, Enkelejda MIHO, Cédric WEBER, René RIEDEL, Skylar COOK, Atijeh VALAI, Telma LOPES, Andreas RADBRUCH, Thomas H. WINKLER und Sai T. REDDY, 2017. Systems analysis reveals high genetic and antigen-driven predetermination of antibody repertoires throughout B cell development. Cell Reports. 16 Mai 2017. Bd. 19, Nr. 7, S. 1467–1478. DOI 10.1016/j.celrep.2017.04.054. Verfügbar unter: https://doi.org/10.26041/fhnw-9966

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