Locus architecture and RAG scanning determine antibody diversity.
Trends Immunol
; 44(2): 119-128, 2023 02.
Article
en En
| MEDLINE
| ID: mdl-36706738
ABSTRACT
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 VH gene usage during V(D)J recombination, shaping the preselected repertoire.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Recombinación V(D)J
/
Diversidad de Anticuerpos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article