High-Throughput Sequencing of the Zebrafish Antibody Repertoire

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Science  08 May 2009:
Vol. 324, Issue 5928, pp. 807-810
DOI: 10.1126/science.1170020

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Antibody Repertoire Revealed

Antibodies produced by B cells protect us against infection by a wide array of pathogens. Such wide-ranging responses are possible because the specific domain of the antibody that binds to the invader is highly variable owing to the somatic recombination of an inherited set of gene segments that encode the antibody molecule. Although antibody diversity within an individual organism is well-established, the specific antibody repertoire of an individual organism has not been characterized. Using high-throughput sequencing technology, Weinstein et al. (p. 807) characterized the diversity of the antigen-binding domain of the antibody heavy chain in zebrafish. The antibody repertoire of individual fish covered at least 50% of the possible gene combinations. Although the specific gene combinations differed between fish, a similar frequency distribution of the repertoire was observed. Unexpected examples of evolutionary conversion were also seen, with the same antibody observed in different animals.


Despite tremendous progress in understanding the nature of the immune system, the full diversity of an organism’s antibody repertoire is unknown. We used high-throughput sequencing of the variable domain of the antibody heavy chain from 14 zebrafish to analyze VDJ usage and antibody sequence. Zebrafish were found to use between 50 and 86% of all possible VDJ combinations and shared a similar frequency distribution, with some correlation of VDJ patterns between individuals. Zebrafish antibodies retained a few thousand unique heavy chains that also exhibited a shared frequency distribution. We found evidence of convergence, in which different individuals made the same antibody. This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism.

  • * These authors contributed equally to this work.

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