Locus suicide recombination actively occurs on the functionally rearranged IgH allele in B-cells from inflamed human lymphoid tissues

by Iman Dalloul, Fran çois Boyer, Zeinab Dalloul, Amandine Pignarre, Gersende Caron, Thierry Fest, Fabrice Chatonnet, Céline Delaloy, Anne Durandy, Robin Jeannet, Emilie Lereclus, Hend Boutouil, Jean-Claude Aldigier, Sophie Péron, Sandrine Le Noir, Jeanne Cook-Moreau, Michel Cogné B-cell activation yields abundant cell death in parallel to clonal amplification and remodeling of immunoglobulin (Ig) genes by activation-induced deaminase (AID). AID promotes affinity maturation of Ig variable regions and class switch recombination (CSR) in mature B lymphocytes. In the IgH locus , these processes are under control of the 3’ regulatory region (3’RR) super-enhancer, a region demonstrated in the mouse to be both transcribed and itself targeted by AID-mediated recombination. Alternatively to CSR, IgH deletions joining Sμ to “like-switch” DNA repeats that flank the 3’ super-enhancer can thus accomplish so-called “locus suicide recombination” (LSR) in mouse B-cells. Using an optimized LSR-seq high throughput method, we now show that AID-mediated LSR is evolutionarily conserved and also actively occurs in humans, providing an activation-induced cell death path way in multiple conditions of B-cell activation. LSR either focuses on the functional IgH allele or is bi-allelic, and its signature is mainly detected when LSR is ongoing while it vanishes from fully differentiated plasma cells or from “resting” blood memory B-cells. Highly diversified breakpoi nts are dist...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research
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