Determinism and stochasticity during maturation of the zebrafish antibody repertoire

Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5348-53. doi: 10.1073/pnas.1014277108. Epub 2011 Mar 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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*

Substances

  • Antibodies
  • Immunoglobulin Subunits
  • Immunoglobulin Variable Region