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Science 5 April 2002:
Vol. 296. no. 5565, pp. 158 - 162
DOI: 10.1126/science.1068768
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Reports

Subnuclear Compartmentalization of Immunoglobulin Loci During Lymphocyte Development

Steven T. Kosak,1* Jane A. Skok,3 Kay L. Medina,1 Roy Riblet,4 Michelle M. Le Beau,2 Amanda G. Fisher,3 Harinder Singh1dagger

Immunoglobulin (Ig) loci are selectively activated for transcription and rearrangement during B lymphocyte development. Using fluorescence in situ hybridization, we show that Ig heavy (H) and Igkappa loci are preferentially positioned at the nuclear periphery in hematopoietic progenitors and pro-T cells but are centrally configured in pro-B nuclei. The inactive loci at the periphery do not associate with centromeric heterochromatin. Upon localization away from the nuclear periphery in pro-B cells, the IgH locus appears to undergo large-scale compaction. We suggest that subnuclear positioning represents a novel means of regulating transcription and recombination of IgH and Igkappa loci during lymphocyte development.

1 Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute,
2 Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
3 Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, UK.
4 Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
*   Present address: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.

dagger    To whom correspondence should be addressed. E-mail: hsingh{at}midway.uchicago.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)