A role for AID in chromosome translocations between c-myc and the IgH variable region

Chromosome translocations between oncogenes and the region spanning the immunoglobulin ( Ig) heavy chain ( IgH) variable ( V), diversity ( D), and joining ( J) gene segments ( Ig V-J(H) region) are found in several mature B cell lymphomas in humans and mice. The breakpoints are frequently adjacent to the recombination signal sequences targeted by recombination activating genes 1 and 2 during antigen receptor assembly in pre-B cells, suggesting that these translocations might be the result of aberrant V( D) J recombination. However, in mature B cells undergoing activation-induced cytidine deaminase ( AID)-dependent somatic hypermutation ( SHM), duplications or deletions that would necessitate a double-trand break make up 6% of all the Ig V-J(H) region -associated somatic mutations. Furthermore, DNA breaks can be detected at this locus in B cells undergoing SHM. To determine whether SHM might induce c-myc to Ig V-J(H) translocations, we searched for such events in both interleukin ( IL) 6 transgenic ( IL-6 tg) and AID(-/)-IL-6 tg mice. Here, we report that AID is required for c-myc to Ig V-J H translocations induced by IL-6.