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-strand 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.
Dorsett
Yair
Y
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
Robbiani
Davide F
DF
Jankovic
Mila
M
Reina-San-Martin
Bernardo
B
Eisenreich
Thomas R
TR
Nussenzweig
Michel C
MC
D000818:Animals; D019457:Chromosome Breakage; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003564:Cytidine Deaminase / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015850:Interleukin-6 / Q000172:deficiency; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D015850:Interleukin-6; D016271:Proto-Oncogene Proteins c-myc; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase