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The Journal of Immunology, 2004, 172: 5851-5860.
Copyright © 2004 by The American Association of Immunologists

Evolutionary Origins of Lymphocytes: Ensembles of T Cell and B Cell Transcriptional Regulators in a Cartilaginous Fish1

Michele K. Anderson2,*, Rashmi Pant*, Ann L. Miracle3,{dagger}, Xiao Sun4,*, Carl A. Luer{ddagger}, Catherine J. Walsh{ddagger}, Janice C. Telfer§, Gary W. Litman{dagger} and Ellen V. Rothenberg5,*

* Division of Biology, California Institute of Technology, Pasadena, CA 91125; {dagger} University of South Florida, Department of Pediatrics, Children’s Research Institute, St. Petersburg, FL 33701; {ddagger} Mote Marine Laboratory, Sarasota, FL 34236; and § Department of Veterinary and Animal Sciences, Paige Laboratory, University of Massachusetts, Amherst, MA 01003

The evolutionary origins of lymphocytes can be traced by phylogenetic comparisons of key features. Homologs of rearranging TCR and Ig (B cell receptor) genes are present in jawed vertebrates, but have not been identified in other animal groups. In contrast, most of the transcription factors that are essential for the development of mammalian T and B lymphocytes belong to multigene families that are represented by members in the majority of the metazoans, providing a potential bridge to prevertebrate ancestral roles. This work investigates the structure and regulation of homologs of specific transcription factors known to regulate mammalian T and B cell development in a representative of the earliest diverging jawed vertebrates, the clearnose skate (Raja eglanteria). Skate orthologs of mammalian GATA-3, GATA-1, EBF-1, Pax-5, Pax-6, Runx2, and Runx3 have been characterized. GATA-3, Pax-5, Runx3, EBF-1, Spi-C, and most members of the Ikaros family are shown throughout ontogeny to be 1) coregulated with TCR or Ig expression, and 2) coexpressed with each other in combinations that for the most part correspond to known mouse T and B cell patterns, supporting conservation of function. These results indicate that multiple components of the gene regulatory networks that operate in mammalian T cell and B cell development were present in the common ancestor of the mammals and the cartilaginous fish. However, certain factors relevant to the B lineage differ in their tissue-specific expression patterns from their mouse counterparts, suggesting expanded or divergent B lineage characteristics or tissue specificity in these animals.


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