Miho, Enkelejda
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Enkelejda
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Miho, Enkelejda
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- PublikationSystems analysis reveals high genetic and antigen-driven predetermination of antibody repertoires throughout B cell development(CellPress, 16.05.2017) Greiff, Victor; Menzel, Ulrike; Miho, Enkelejda; Weber, Cédric; Riedel, René; Cook, Skylar; Valai, Atijeh; Lopes, Telma; Radbruch, Andreas; Winkler, Thomas H.; Reddy, Sai T. [in: Cell Reports]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.01A - Beitrag in wissenschaftlicher Zeitschrift