PUBLICATION
Determinism and stochasticity during maturation of the zebrafish antibody repertoire
- Authors
- Jiang, N., Weinstein, J.A., Penland, L., White, R.A., Fisher, D.S., and Quake, S.R.
- ID
- ZDB-PUB-110325-14
- Date
- 2011
- Source
- Proceedings of the National Academy of Sciences of the United States of America 108(13): 5348-53 (Journal)
- Registered Authors
- Keywords
- immunology, repertoire development, secondary repertoire
- MeSH Terms
-
- Adaptive Immunity/physiology*
- Animals
- Antibodies/genetics*
- Antibody Diversity*
- Immunoglobulin Subunits/genetics
- Immunoglobulin Variable Region/genetics
- Stochastic Processes*
- VDJ Exons
- Zebrafish/genetics
- Zebrafish/immunology*
- PubMed
- 21393572 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Jiang, N., Weinstein, J.A., Penland, L., White, R.A., Fisher, D.S., and Quake, S.R. (2011) Determinism and stochasticity during maturation of the zebrafish antibody repertoire. Proceedings of the National Academy of Sciences of the United States of America. 108(13):5348-53.
Abstract
It is thought that the adaptive immune system of immature organisms follows a more deterministic program of antibody creation than is found in adults. We used high-throughput sequencing to characterize the diversifying antibody repertoire in zebrafish over five developmental time points. We found that the immune system begins in a highly stereotyped state with preferential use of a small number of V (variable) D (diverse) J (joining) gene segment combinations, but that this stereotypy decreases dramatically as the zebrafish mature, with many of the top VDJ combinations observed in 2-wk-old zebrafish virtually disappearing by 1 mo. However, we discovered that, in the primary repertoire, there are strong correlations in VDJ use that increase with zebrafish maturity, suggesting that VDJ recombination involves a level of deterministic programming that is unexpected. This stereotypy is masked by the complex diversification processes of antibody maturation; the variation and lack of correlation in full repertoires between individuals appears to be derived from randomness in clonal expansion during the affinity maturation process. These data provide a window into the mechanisms of VDJ recombination and diversity creation and allow us to better understand how the adaptive immune system achieves diversity.
Errata / Notes
White, R.A. III
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping