Molecular analysis of DNA rearrangements in the immune system

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The vertebrate immune system is unique among multicellular organisms, featuring both nonspecific immunity and a diverse array of millions of antigen receptors, including immunoglobulins and T-cell receptors. A critical subset of these receptors binds to invading microbes or their biochemicals, marking them for elimination. Three essential DNA modification processes facilitate this in vertebrates. V(D)J recombination is responsible for generating the exons that encode antigen binding pockets, and recent research has elucidated this process at the biochemical level, identifying the proteins that catalyze its steps through biochemical and genetic analysis. Class switch recombination allows the heavy chain's variable domain exon to switch from IgM to IgG, IgA, or IgE, with recent advancements in an extrachromosomal substrate assay system and molecular genetic analysis in transgenics revealing cis sequence requirements. Additionally, biochemical assays have been developed to define enzymatic components involved in these processes. Exciting progress has also been made in understanding somatic hypermutation, highlighting the ongoing advancements in the field of immune system research.