Determinism and Stochasticity During Maturation of the Zebrafish Antibody Repertoire

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 Mar 12

PMID 21393572

Citations 60

Authors

Ning Jiang

Joshua A Weinstein

Lolita Penland

Richard A White 3rd

Daniel S Fisher

Stephen R Quake

Affiliations

Soon will be listed here.

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.

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