Figure 3.

Locus contraction at antigen-receptor loci maximizes receptor diversity. Megabase-sized antigen-receptor loci (e.g. the murine immunoglobulin kappa locus shown here) are organized in TADs. Differentiation signals induce B-to-A compartment switching of the locus and trigger the establishment of a 3′-end recombination center near the (D-)J elements. At the recombination center, B-cell transcription factors (TFs) create an active chromatin environment that facilitates the recruitment of the RAG1/RAG2 V(D)J recombinase. To ensure equal average proximity of all V genes to the recombination center, antigen-receptor loci ‘contract’ to create a compact 3D structure that provides largely equal opportunities for every V gene to be recombined.