Determinism and stochasticity during maturation of the zebrafish antibody repertoire

作者：Jiang Ning; Weinstein Joshua A; Penland Lolita; White Richard A III; Fisher Daniel S; Quake Stephen R^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(13): 5348-5353.

DOI：10.1073/pnas.1014277108

• immunology
• repertoire development
• secondary repertoire

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.

• 出版日期2011-3-29