Epigenetics of the Immune System

Abstract The various cells of the immune system all originate from the hematopoietic stem cell, yet each serves a distinct function in the immune response. The differentiation process of the immune system is multistaged and, in the adaptive immune system, includes defined steps of targeted mutations in the genome, such as V(D)J recombination of antigen receptors in B and T cells, and somatic hypermutations at the variable region of the immunoglobulin receptors. Epigenetic marks, such as DNA methylation, histone modifications, chromatin topology, subnuclear localization and replication timing, regulate the accessibility and the stable expression or repression of genomic loci. In this chapter, in which attention is focused on the adaptive immune system, the role of epigenetic marks is discussed in the regulation of the various stages of immune cell development. This discussion sequence includes the potentiation of various cell lineages in hematopoietic stem cells, the stepwise activation and repression of key loci during the differentiation process, the targeting of somatic mutations and, finally, the stable commitment of cellular expression programs in fully differentiated cells.