Conserved Functions of Ikaros in Vertebrate Lymphocyte Development: Genetic Evidence for Distinct Larval and Adult Phases of T Cell Development and Two Lineages of B Cells in Zebrafish

Zebrafish has been advocated as an alternative animal model to study lymphocyte development, although the similarities in the genetic requirements of lymphopoiesis between fish and mammals have not yet been investigated. In this study, we examine the role of the transcription factor Ikaros in zebraf...

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Bibliographic Details
Published in:Journal of Immunology 2006-08, Vol.177 (4), p.2463-2476
Main Authors: Schorpp, Michael, Bialecki, Mike, Diekhoff, Dagmar, Walderich, Brigitte, Odenthal, Jorg, Maischein, Hans-Martin, Zapata, Agustin G, Tubingen 2000 Screen Consortium, Freiburg Screening Group, Boehm, Thomas
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Sequence
Animals
B-Lymphocytes - cytology
B-Lymphocytes - immunology
Base Sequence
Cell Differentiation - genetics
Cell Differentiation - immunology
Cell Lineage - genetics
Cell Lineage - immunology
Codon, Nonsense
Conserved Sequence
Danio rerio
Ikaros Transcription Factor - genetics
Ikaros Transcription Factor - physiology
Larva
Male
Molecular Sequence Data
Phenotype
Receptors, CCR
Receptors, Chemokine - genetics
T-Lymphocytes - cytology
T-Lymphocytes - immunology
Zebrafish - growth & development
Zebrafish - immunology
Zebrafish Proteins - genetics
Zebrafish Proteins - physiology
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Summary:Zebrafish has been advocated as an alternative animal model to study lymphocyte development, although the similarities in the genetic requirements of lymphopoiesis between fish and mammals have not yet been investigated. In this study, we examine the role of the transcription factor Ikaros in zebrafish lymphopoiesis. In fish larvae homozygous for an ikaros allele predicted to lack the C-terminal zinc fingers, T lymphopoiesis is absent; the presence of V(H)DmuJmu rearrangements in adolescent fish is delayed in mutants. In adolescent mutant fish, T cells expressing tcrb and tcrd and B cells expressing igm are formed with low efficiency and display an oligoclonal Ag receptor repertoire. By contrast, B cells expressing the igz isotype do not develop, providing genetic evidence for two separate B cell lineages in zebrafish. Thus, Ikaros appears to play similar roles in fish and mammalian lymphopoiesis.
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.177.4.2463