Locus architecture and RAG scanning determine antibody diversity.

Autor: Kenter AL; Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612-7344, USA. Electronic address: star1@uic.edu., Priyadarshi S; Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612-7344, USA., Drake EB; Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612-7344, USA.
Jazyk: angličtina
Zdroj: Trends in immunology [Trends Immunol] 2023 Feb; Vol. 44 (2), pp. 119-128.
DOI: 10.1016/j.it.2022.12.005
Abstrakt: Diverse mammalian antibody repertoires are produced via distant genomic contacts involving immunoglobulin Igh variable (V), diversity (D), and joining (J) gene segments and result in V(D)J recombination. How such interactions determine V gene usage remains unclear. The recombination-activating gene (RAG) chromatin scanning model posits that RAG recombinase bound to the recombination center (RC) linearly tracks along chromatin by means of cohesin-mediated loop extrusion; a proposition supported by cohesin depletion studies. A mechanistic role for chromatin loop extrusion has also been implicated for Igh locus contraction. In this opinion, we provide perspective on how loop extrusion interfaces with the 3D conformation of the Igh locus and newly identified enhancers that regionally regulate V H gene usage during V(D)J recombination, shaping the preselected repertoire.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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