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The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z

Nature Immunology volume 6, pages 295–302 (2005)Cite this article

Abstract

The only immunoglobulin heavy-chain classes known so far in teleosts have been μ and δ. We identify here a previously unknown class, immunoglobulin ζ, expressed in zebrafish and other teleosts. In the zebrafish heavy-chain locus, variable (V) gene segments lie upstream of two tandem diversity, joining and constant (DJC) clusters, resembling the mouse T cell receptor α (Tcra) and δ (Tcrd) locus. V genes rearrange to (DJC)ζ or to (DJC)μ without evidence of switch rearrangement. The zebrafish immunoglobulin ζ gene (ighz) and mouse Tcrd, which are proximal to the V gene array, are expressed earlier in development. In adults, ighz was expressed only in kidney and thymus, which are primary lymphoid organs in teleosts. This additional class adds complexity to the immunoglobulin repertoire and raises questions concerning the evolution of immunoglobulins and the regulation of the differential expression of ighz and ighm.

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Figure 1: Zebrafish igh locus.
Figure 2: Zebrafish igh locus versus mouse Tcra-Tcrd and Igh loci.
Figure 3: Unrooted phylogentic tree of immunoglobulin C region sequences.
Figure 4: DH and JH usage in zebrafish expressed μ and ζ.
Figure 5: Expression of igm and igz during development.
Figure 6: Expression of igm and igz in zebrafish organs.

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Acknowledgements

We thank C. Rexroad and R. Athey of the US Department of Agriculture National Center for Cool and Cold Water Aquaculture Research Center for providing the rainbow trout cDNA clones. Supported in part by the National Institutes of Health (R01 AI08054).

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Author notes

  1. Jeroen Bussmann

    Present address: Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands

  2. Nadia Danilova and Jeroen Bussmann: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Nadia Danilova, Jeroen Bussmann & Lisa A Steiner

  2. The Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK

    Kerstin Jekosch

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  1. Nadia Danilova
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Correspondence to Lisa A Steiner.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Southern blot analysis of zebrafish genomic DNA with Cμ probe. (PDF 136 kb)

Supplementary Fig. 2

Classification of VH families. (PDF 216 kb)

Supplementary Fig. 3

Unrooted phylogenetic tree of VH sequences. (PDF 142 kb)

Supplementary Fig. 4

Alignment of the amino acid sequences encoded by Cμ and Cζ of zebrafish and other species. (PDF 152 kb)

Supplementary Fig. 5

A conserved sequence in the Cμ-Cδ intergenic region. (PDF 179 kb)

Supplementary Table 1

V, D and J gene segments in the zebrafish igh locus (PDF 125 kb)

Supplementary Table 2

Tools and databases used in the identification of igh genes (PDF 104 kb)

Supplementary Table 3

Comparison of CDR3 regions of μ and ζ cDNA and genomic cDNA (PDF 109 kb)

Supplementary Table 4

Primers (PDF 65 kb)

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Danilova, N., Bussmann, J., Jekosch, K. et al. The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z. Nat Immunol 6, 295–302 (2005). https://doi.org/10.1038/ni1166

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