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.

Keywords

Systems immunology, Lg-seq, Bioinformatics

Subject (DDC)

600 - Technik, Medizin, angewandte Wissenschaften

Project

Event

Exhibition start date

Exhibition end date

Conference start date

Conference end date

Date of the last check

ISBN

ISSN

2211-1247
2639-1856

Language

English

Created during FHNW affiliation

No

Strategic action fields FHNW

Publication status

Published

Review

Peer review of the complete publication

Open access category

Gold

License

Citation

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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