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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 Zebrafish¹

Michael Schorpp^2,*, Mike Bialecki^2,*, Dagmar Diekhoff^*, Brigitte Walderich^3,, Jörg Odenthal^4,, Hans-Martin Maischein, Agustin G. Zapata Tübingen 2000 Screen Consortium⁵ Freiburg Screening Group⁵, Thomas Boehm^6,*

^* Department of Developmental Immunology, Max-Planck Institute of Immunobiology, Freiburg, Germany; Exelixis Germany, Tübingen, Germany; Department of Genetics, Max-Planck Institute of Developmental Biology, Tübingen, Germany; and Department of Cell Biology, Complutense University, Madrid, Spain

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_HDµJµ 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.

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