Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development
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Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development. / 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 REP, Vol. 19, No. 7, 16.05.2017, p. 1467-1478.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development
AU - Greiff, Victor
AU - Menzel, Ulrike
AU - Miho, Enkelejda
AU - Weber, Cédric
AU - Riedel, René
AU - Cook, Skylar
AU - Valai, Atijeh
AU - Lopes, Telma
AU - Radbruch, Andreas
AU - Winkler, Thomas H
AU - Reddy, Sai T
N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2017/5/16
Y1 - 2017/5/16
N2 - 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.
AB - 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.
KW - Animals
KW - Antibodies/metabolism
KW - Antigens/metabolism
KW - B-Lymphocytes/metabolism
KW - Cell Proliferation
KW - Clone Cells
KW - Germ Cells/metabolism
KW - Mice, Inbred C57BL
KW - Plasma Cells/metabolism
KW - Systems Analysis
U2 - 10.1016/j.celrep.2017.04.054
DO - 10.1016/j.celrep.2017.04.054
M3 - SCORING: Journal article
C2 - 28514665
VL - 19
SP - 1467
EP - 1478
JO - CELL REP
JF - CELL REP
SN - 2211-1247
IS - 7
ER -
