The Journal of Experimental Medicine
CSHL 2010 Immunology Conference
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Published online 15 May 2000.
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© The Rockefeller University Press, 0022-1007/2000/5/1637/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 10, May 15, 2000 1637-1648

Original Article

Rearrangement of Immunoglobulin Genes in Shark Germ Cells

Susan S. Leea, David Fitchb, Martin F. Flajnikc, and Ellen Hsua

a Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203
b Department of Biology, New York University, New York, New York 10003
c Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland 21201
Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, 450 Clarkson Ave., Brooklyn, NY 11203.718-270-3103718-270-1154

hsue{at}hscbklyn.edu

The variable (V), (diversity [D]), and joining (J) region recombinases (recombination activating genes [RAGs]) can perform like transposases and are thought to have initiated development of the adaptive immune system in early vertebrates by splitting archaic V genes with transposable elements. In cartilaginous fishes, the immunoglobulin (Ig) light chain genes are organized as multiple VJ-constant (C) clusters; some loci are capable of rearrangement while others contain fused VJ. The latter may be key to understanding the evolutionary role of RAG. Are they relics of the archaic genes, or are they results of rearrangement in germ cells? Our data suggest that some fused VJ genes are not only recently rearranged, but also resulted from RAG-like activity involving hairpin intermediates. Expression studies show that these, like some other germline-joined Ig sequences, are expressed at significant levels only early in ontogeny. We suggest that a rejoined Ig gene may not merely be a sequence restricting antibody diversity, but is potentially a novel receptor no longer tied to somatic RAG expression and rearrangement. From the combined data, we arrived at the unexpected conclusion that, in some vertebrates, RAG is still an active force in changing the genome.

Key Words: V(D)J recombination • rearrangement • immunoglobulin genes • light chain • germline joining

Abbreviations used in this paper: FR, framework region; Myr BP, million years before present; RAG, recombination activating gene; RSS, recombination signal sequence(s); RT, reverse transcription; TdT, terminal deoxynucleotidyl transferase.

© 2000 The Rockefeller University Press


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