Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development

Greiff V, Menzel U, Miho E, Weber C, Riedel R, Cook S, Valai A, Lopes T, Radbruch A, Winkler T, Reddy ST (2017)


Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2017

Journal

Publisher: Elsevier B.V.

Book Volume: 19

Pages Range: 1467-1478

Journal Issue: 7

DOI: 10.1016/j.celrep.2017.04.054

Abstract

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.

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APA:

Greiff, V., Menzel, U., Miho, E., Weber, C., Riedel, R., Cook, S.,... 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://dx.doi.org/10.1016/j.celrep.2017.04.054

MLA:

Greiff, Victor, et al. "Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development." Cell Reports 19.7 (2017): 1467-1478.

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