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.
Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development.
Victor Greiff,U. Menzel,Enkelejda Miho,Cédric R. Weber,R. Riedel,Skylar C. Cook,Atijeh Valai,Telma Lopes,Andreas Radbruch,T. Winkler,S. Reddy
Published 2017 in Cell Reports
ABSTRACT
PUBLICATION RECORD
- Publication year
2017
- Venue
Cell Reports
- Publication date
2017-05-16
- Fields of study
Biology, Medicine, Computer Science
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- antibody repertoire components
The repertoire features quantified in the analysis, including V-gene usage, clonal expansion, clonal diversity, and repertoire size.
Aliases: repertoire components
- antibody repertoire sequencing data
High-throughput sequencing reads of antibody repertoires used to quantify repertoire features in the study.
Aliases: antibody-repertoire sequencing data, repertoire sequencing data
- antigen-driven predetermination
The component of repertoire variation attributed to antigen exposure in the analysis.
Aliases: antigen dependent predetermination
- antigen exposure
Exposure to three structurally different proteins used as the antigenic comparison axis in the analysis.
Aliases: antigenic exposure
- b cell development
The developmental progression of B cells from pre-B cell through naive B cell to plasma cell stages used as one axis of comparison.
Aliases: B-cell development
- clonal diversity
The diversity of clonotypes present within a repertoire sample.
Aliases: clone diversity
- clonal expansion
The expansion of related B cell clones represented by repeated antibody sequences in a repertoire sample.
Aliases: clone expansion
- genetic predetermination
The component of repertoire variation attributed to inherited or developmental constraints in the analysis.
Aliases: genetically predetermined component
- naive b cell
An antigen-inexperienced B cell stage included in the developmental comparison.
Aliases: naive B cells
- plasma cell
An antibody-secreting differentiated B cell stage included in the developmental comparison.
Aliases: plasma cells
- repertoire size
The total number of distinct antibody repertoire elements measured in a sample.
Aliases: antibody repertoire size
- stochastic variation
The residual non-deterministic variation in repertoire features after genetic and antigen-related effects are considered.
Aliases: random variation
- systems immunology framework
An analysis framework that combines immune repertoire measurements with systems-level quantification across defined biological contexts.
Aliases: systems-immunology framework
- v-gene usage
The distribution of immunoglobulin V-gene segment usage across the antibody repertoire.
Aliases: V gene usage, variable-gene usage
REFERENCES
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