Greiff, VictorMenzel, UlrikeMiho, EnkelejdaWeber, CédricRiedel, RenéCook, SkylarValai, AtijehLopes, TelmaRadbruch, AndreasWinkler, Thomas H.Reddy, Sai T.2024-08-162024-08-162017-05-162211-12472639-185610.1016/j.celrep.2017.04.054https://irf.fhnw.ch/handle/11654/46942https://doi.org/10.26041/fhnw-9966Antibody 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.enSystems immunologyLg-seqBioinformatics600 - Technik, Medizin, angewandte WissenschaftenSystems analysis reveals high genetic and antigen-driven predetermination of antibody repertoires throughout B cell development01A - Beitrag in wissenschaftlicher Zeitschrift1467-1478