Clonal allelic predetermination of immunoglobulin-kappa rearrangement

Although most genes are expressed biallelically, a number of key genomic sites-including immune and olfactory receptor regions-are controlled monoallelically in a stochastic manner, with some cells expressing the maternal allele and others the paternal allele in the target tissue(1,2). Very little is known about how this phenomenon is regulated and programmed during development. Here, using mouse immunoglobulin-kappa (Ig kappa) as a model system, we demonstrate that although individual haematopoietic stem cells are characterized by allelic plasticity, early lymphoid lineage cells become committed to the choice of a single allele, and this decision is then stably maintained in a clonal manner that predetermines monoallelic rearrangement in B cells. This is accompanied at the molecular level by underlying allelic changes in asynchronous replication timing patterns at the kappa locus. These experiments may serve to define a new concept of stem cell plasticity.