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Determinism and stochasticity during maturation of the zebrafish antibody repertoire
Ning Jiang, Joshua A. Weinstein, Lolita Penland, Richard A. White III, Daniel S. Fisher, Stephen R. Quake and Steven H. Kleinstein
Proceedings of the National Academy of Sciences of the United States of America
Vol. 108, No. 13 (March 29, 2011), pp. 5348-5353
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/41125702
Page Count: 6
You can always find the topics here!Topics: Antibodies, Age groups, Sequencing, Stereotypies, B lymphocytes, Amino acids, Beta cells, Genetic mutation, Adaptive immunity, Adults
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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.
Proceedings of the National Academy of Sciences of the United States of America © 2011 National Academy of Sciences