Certain cells of the immune system more readily tolerate damage to their genes than do other cells, up to a point. New research in Nature Immunology shows the protein BCL6, expressed in antibody-producing B cells, senses how much DNA damage is occurring inside these cells and activates repair pathways when damage becomes excessive.
BCL6 is a repressor that blocks expression of DNA repair enzymes in the presence of small amounts of damage. This suppression is beneficial to the B cells as these cells can 'fine-tune' their antibody responses by mutating the antibody genes or undergoing what is called 'class switch recombination', a genetic rearrangement that allows different types of antibodies to be produced.
Riccardo Dalla-Favera and colleagues show excessive DNA damage in these B cells can be recognized by BCL6. BCL6 acts as a 'damage-sensitive' resistor that, once tipped beyond a threshold amount of accumulated DNA breaks, initiates a pathway that leads to its own destruction and turns on repair enzymes. These findings further our understanding of BCL6, which is commonly found to be mutated in forms of B cell cancers, and may thereby be instructive in designing therapies to blunt BCL6 activity in these cancers.
Riccardo Dalla-Favera (Columbia University, New York, NY, USA)
Abstract available online.
(C) Nature Immunology press release.
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