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

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Science  18 May 2012:
Vol. 336, Issue 6083, pp. 931-934
DOI: 10.1126/science.1218692

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Suicidal B cells

In response to an infection, immunological B cells undergo a maturation process that results in the production of immunoglobulin (Ig) that is better able to bind and clear the invading pathogen. This occurs through somatic cell hypermutation and class switch recombination of the Ig gene and requires activation-induced deaminase (AID). Péron et al. (p. 931, published online 26 April) observed that the 3' cis-regulatory region of the heavy-chain locus is transcribed and undergoes AID-mediated mutation and recombination. The resulting deletion of the Ig heavy gene cluster generates B cells that are no longer able to express Ig on the cell surface. Because cell-surface Ig expression is essential for B cell survival, this process is termed “locus suicide recombination” (LSR) and may be important in shaping the dynamics of B effector cell differentiation and homeostasis.

Abstract

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 switchlike 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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