Immunoglobulin locus silencing and allelic exclusion

Abstract

Lymphocytes are characterised by monoclonal expression of antigen receptors. This is achieved by silencing of one of two homologous antigen receptor alleles, a process known as allelic exclusion. This process is regulated both before and after V(D)J recombination, by a variety of mechanisms. These include nuclear localisation, changes in chromatin structure and histone modifications, non-coding sense and antisense RNA transcription, epigenetic alterations at the DNA level, feedback signalling from expressed alleles, locus contraction and decontraction, recruitment to heterochromatin. This review will focus on recent advances in the immunoglobulin heavy and kappa light chain loci. The current picture is of a complex, temporally ordered sequence of events, in which these loci share many contributory mechanisms, but clear and intriguing differences are emerging.