AID-Driven Deletion Causes Immunoglobulin Heavy Chain “Locus Suicide Recombination” in B Cells

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Science  26 Apr 2012:
DOI: 10.1126/science.1218692

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Remodeling of immunoglobulin genes by activation-induced deaminase (AID) is required for affinity maturation and class switch recombination in mature B lymphocytes. In the immunoglobulin heavy chain locus, these processes are predominantly controlled by the 3′ cis-regulatory region. We now show that this region is transcribed and undergoes AID-mediated mutation and recombination around phylogenetically conserved switch-like DNA repeats. Such recombination, which we term “locus suicide recombination,” deletes the whole constant region gene cluster and thus stops expression of the immunoglobulin of the B cell surface, which is critical for B cell survival. The frequency of this event is approaching that of class switching and makes it a potential regulator of B cell homeostasis.

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