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HYPOTHESIS AND THEORY article

Front. Immunol.

Sec. B Cell Biology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1678105

This article is part of the Research TopicGene Regulation in Lymphocyte Development and ResponseView all 7 articles

Exuberant long noncoding RNA expression may sculpt Igh locus topology

Provisionally accepted
Ellen Brandenburg DrakeEllen Brandenburg Drake1Sarah NaiyerSarah Naiyer1Xinyan QuXinyan Qu1Khalid BhatKhalid Bhat1Hammad FarooqHammad Farooq2Mark Maienschein-ClineMark Maienschein-Cline3Jie LiangJie Liang2Amy L KenterAmy L Kenter1*
  • 1Microbiology and Immunology, University of Illinois Chicago, Chicago, Illinois, United States
  • 2Department of Biomedical Engineering, University of Illinois Chicago, Chicago, Illinois, United States
  • 3Research Informatics Core, Research Resources Center, University of Illinois Chicago, Chicago, Illinois, United States

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Diverse Igh repertoires require successful V(D)J recombination allowing B cell receptor expression and Ig secretion for humoral immune responses. Igh locus contraction has been implicated in generating spatial proximity between distal VH segments and the recombination center via cohesin mediated loop extrusion. However, it remains unclear why some distal VH segments recombine with high frequency while other more proximal VH are rarely used. Long non-coding RNAs (lncRNAs) have emerged as regulators of cellular development, differentiation and gene expression. Here we report exceptionally high expression of lncRNAs at the Igh locus and other AgR loci engaged in V(D)J recombination. A tight correlation was found between positions of multi-exonic lncRNAs, Igh enhancers and chromatin loop anchors. We propose an integrated model of factors including lncRNAs and loop extrusion in determining Igh locus topology and VH gene usage during recombination.

Keywords: Progenitor B cells, V(D)J Recombination, IgH locus, Chromatin folding, long non-coding RNA

Received: 01 Aug 2025; Accepted: 21 Oct 2025.

Copyright: © 2025 Drake, Naiyer, Qu, Bhat, Farooq, Maienschein-Cline, Liang and Kenter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Amy L Kenter, star1@uic.edu

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material