Advances in the Mechanistic Understanding of Chromatin Loop Extrusion in Antigen Receptor Diversification
JIAO Fangtai, LUO Rui, DING Xuxu, YANG Dingpeng, DAI Hai-Qiang*
Antigen receptor diversification is a central feature of the adaptive immune system and is
primarily generated through V(D)J recombination during B- and T-cell development. In recent years, chromatinloop extrusion has emerged as a key mechanism regulating the three-dimensional organization of antigenreceptor loci and the efficiency of recombination. This review summarizes recent advances in understanding how cohesin-mediated loop extrusion regulates V(D)J recombination in B and T cells. They discuss its roles during lymphocyte development in the bone marrow and thymus, with a particular focus on the temporal and spatial regulation of V(D)J recombination at the mouse Igh (immunoglobulin heavy chain) locus. In addition, they review how transcription factors and epigenetic modifications modulate loop extrusion dynamics, and they examine the potential links between dysregulated loop extrusion, immunodeficiency, and lymphoid malignancies. Finally, they highlight key unresolved questions and future directions in this rapidly evolving field. A deeper understanding of the molecular mechanisms by which chromatin loop extrusion governs antigen receptor diversification will provide insights into the relationship between three-dimensional genome organization and immune function, and may inform new strategies for the treatment of immunodeficiency and lymphoid malignancies.
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