Genetic and epigenetic regulation of IgH gene assembly

Precursor B cells assemble a diverse repertoire of immunoglobulin (Ig) genes by the process of V(D)J recombination. Assembly of IgH genes is regulated in a tissue- and stage-specific manner via the activation and then the inactivation of distinct regions within the one megabase IgH locus. Recent studies have shown that regional control is achieved using a combination of genetic and epigenetic strategies, which modulate chromatin accessibility to V(D)J recombinase, relocate IgH loci within the nucleus, and promote changes in locus conformation that alter the spatial proximity of target gene segments. Orchestration of these regulatory processes is crucial for the generation of a functional B cell repertoire.