Subnuclear Compartmentalization of Immunoglobulin Loci During Lymphocyte Development

TLDR

Immunoglobulin loci are selectively activated for transcription and rearrangement during B lymphocyte development. The study proposes that subnuclear positioning regulates transcription and recombination of IgH and Igκ loci during lymphocyte development. Fluorescence in situ hybridization revealed that IgH and Igκ loci are positioned at the nuclear periphery in hematopoietic progenitors and pro‑T cells, but centrally in pro‑B cells. IgH and Igκ loci are positioned at the nuclear periphery in progenitors and pro‑T cells but centrally in pro‑B cells, where they compact without heterochromatin association, indicating subnuclear positioning regulates their transcription and recombination.

Abstract

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 Igκ 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 Igκ loci during lymphocyte development.