Present understanding of antibodies and their related genes is based almost entirely on information derived from a few mammalian species. The overall goal of this research program is to increase our understanding of the range of diversity in the vertebrate immune system. These investigations may also clarify aspects of the immune response in mammals. Much of our recent work has focussed on the immune system of the amphibian, Xenopus laevis, a classical model for vertebrate development. One objective is to elucidate the genomic organization of a recently identified immunoglobulin light chain family in Xenopus. This family is particularly interesting because it is very different in sequence from all known light chains. Examination of the genes encoding these light chains may provide insight into evolutionary relationships, which are not apparent from sequence comparisons. The developmental sequence of gene rearrangement events in the formation of immunoglobulin and T cell receptor molecules will also be examined. To this end, we have identified the Xenopus homologues of two genes, RAG-1 and RAG-2, which have a critical role in this process. Studies of their expression should help to define developmental lineages of B and T lymphocytes in this species. These studies may also elucidate the molecular basis for changes in the immune response that accompany metamorphosis. Although immunoglobulin genes have been characterized in considerable detail, genes encoding Xenopus T cell receptors have not yet been identified. Therefore, isolation and characterization of these receptors is an important objective. To date, there is no definitive evidence for an inducible immune response in the most primitive vertebrate group, the Agnatha (jawless fish). Since our studies indicate that RAG-1 is a highly conserved gene from sharks to mammals, it may be more easily identified than the more divergent immunoglobulin genes. We will, therefore, determine whether RAG-1 is present in representative Agnatha (hagfish and lamprey); its identification would justify renewed efforts to characterize the immune system of these primitive vertebrates.
| Danilova, N; Saunders, H L; Ellestad, K K et al. (2011) The zebrafish IgH locus contains multiple transcriptional regulatory regions. Dev Comp Immunol 35:352-9 |
| Beetz, Susann; Diekhoff, Dagmar; Steiner, Lisa A (2007) Characterization of terminal deoxynucleotidyl transferase and polymerase mu in zebrafish. Immunogenetics 59:735-44 |
| Danilova, Nadia; Bussmann, Jeroen; Jekosch, Kerstin et al. (2005) The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z. Nat Immunol 6:295-302 |
| Shen, Ching-Hung; Steiner, Lisa A (2004) Genome structure and thymic expression of an endogenous retrovirus in zebrafish. J Virol 78:899-911 |
| Danilova, Nadia; Hohman, Valerie S; Sacher, Frank et al. (2004) T cells and the thymus in developing zebrafish. Dev Comp Immunol 28:755-67 |
| Danilova, Nadia; Visel, Axel; Willett, Catherine E et al. (2004) Expression of the winged helix/forkhead gene, foxn4, during zebrafish development. Brain Res Dev Brain Res 153:115-9 |
| Hohman, Valerie S; Stewart, Sue E; Rumfelt, Lynn L et al. (2003) J chain in the nurse shark: implications for function in a lower vertebrate. J Immunol 170:6016-23 |
| Danilova, Nadia; Steiner, Lisa A (2002) B cells develop in the zebrafish pancreas. Proc Natl Acad Sci U S A 99:13711-6 |
| Willett, C E; Kawasaki, H; Amemiya, C T et al. (2001) Ikaros expression as a marker for lymphoid progenitors during zebrafish development. Dev Dyn 222:694-8 |
| Danilova, N; Hohman, V S; Kim, E H et al. (2000) Immunoglobulin variable-region diversity in the zebrafish. Immunogenetics 52:81-91 |
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