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Lisa A Steiner

Publications and source records attributed to Lisa A Steiner.

7 recordsLinked to original sources

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

The only immunoglobulin heavy-chain classes known so far in teleosts have been mu and delta. We identify here a previously unknown class, immunoglobulin zeta, 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 alpha (Tcra) and delta (Tcrd) locus. V genes rearrange to (DJC)(zeta) or to (DJC)(mu) without evidence of switch rearrangement. The zebrafish immunoglobulin zeta 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.

Animals↗

Expression of the winged helix/forkhead gene, foxn4, during zebrafish development.

The winged-helix/forkhead transcription factor gene, foxn4, is expressed in the nervous system of developing and adult zebrafish. Prominent expression sites include the olfactory placode, the basal layer of the olfactory epithelium, the neuroepithelium of the developing retina, the germinal zone of the differentiated eye, regions of motoneuron development in the neural tube and periventricular regions of the brain. The adult thymus is the only major site of foxn4 expression outside of the nervous system.

Amino Acid Sequence↗

T cells and the thymus in developing zebrafish.

The expression of genes encoding T cell receptor (TCR) alpha was used to follow the development of the thymus and to analyze the distribution of T cells in zebrafish. In the thymus, expression was first detected, by in situ hybridization, at four days post fertilization. In RNA extracted from whole fish, TCRalpha transcripts were also detected at four days and reached adult levels at three weeks. At six weeks, TCRalpha was expressed throughout the thymus, whereas rag1 expression was localized to the peripheral regions. Expression of TCRalpha outside the thymus was detected at nine days. In adult peripheral organs, the greatest expression was in the pronephros, mesonephros and intestine; expression in the spleen became greater as fish age. Three new, relatively highly expressed, TCR Valpha families were identified.

Amino Acid Sequence↗

Genome structure and thymic expression of an endogenous retrovirus in zebrafish.

In a search for previously unknown genes that are required for lymphocyte development in zebrafish, a retroviral sequence was identified in a subtracted thymus cDNA library and in genomic DNA libraries. The provirus is 11.2 kb and contains intact open reading frames for the gag, pol, and env genes, as well as nearly identical flanking long terminal repeat sequences. As determined by in situ hybridization, the thymus appears to be a major tissue for retroviral expression in both larval and adult fish. Several viral transcripts were found by Northern blotting in the adult thymus. The provirus was found at the same genomic locus in sperm from four fish, suggesting that it is an endogenous retrovirus. Phylogenetic analysis indicates that it is closest to, yet distinct from, the cluster of murine leukemia virus-related retroviruses, suggesting that this virus represents a new group of retroviruses.

Animals↗

J chain in the nurse shark: implications for function in a lower vertebrate.

J chain is a small polypeptide covalently attached to polymeric IgA and IgM. In humans and mice, it plays a role in binding Ig to the polymeric Ig receptor for transport into secretions. The putative orthologue of mammalian J chain has been identified in the nurse shark by sequence analysis of cDNA and the polypeptide isolated from IgM. Conservation with J chains from other species is relatively poor, especially in the carboxyl-terminal portion, and, unlike other J chains, the shark protein is not acidic. The only highly conserved segment in all known J chains is a block of residues surrounding an N-linked glycosylation site. Of the eight half-cystine residues that are conserved in mammalian J chains, three are lacking in the nurse shark, including two in the carboxyl-terminal segment that have been reported to be required for binding of human J chain-containing IgA to secretory component. Taken together with these data, the relative abundance of J chain transcripts in the spleen and their absence in the spiral valve (intestine) suggest that J chain in nurse sharks may not have a role in Ig secretion. Analysis of J chain sequences in diverse species is in agreement with accepted phylogenetic relationships, with the exception of the earthworm, suggesting that the reported presence of J chain in invertebrates should be reassessed.

Amino Acid Sequence↗

Alfred Nisonoff.

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Allergy and Immunology↗

B cells develop in the zebrafish pancreas.

The zebrafish, with its transparent free-living embryo, is a useful organism for investigating early stages in lymphopoiesis. Previously, we showed that T cells differentiate in the thymus by day 4, but no sites for B cell differentiation were seen until 3 weeks. We report here that on day 4, we detect rearrangements of genes encoding B cell receptors in DNA extracted from whole fish. Also by day 4, rag1 transcripts are seen in the pancreas, an organ not previously associated with lymphopoiesis; by day 10, Igmu transcripts are detected here. Thus, in zebrafish, the pancreas assumes the role of both the liver in fetal mice and the spleen in neonatal mice.

Animals↗