The Journal of Experimental Medicine
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Published online August 27, 2007
doi:10.1084/jem.20070884
The Journal of Experimental Medicine, Vol. 204, No. 9, 2225-2232
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Dorsett et al.
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ARTICLE

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

Yair Dorsett1, Davide F. Robbiani1, Mila Jankovic1, Bernardo Reina-San-Martin3, Thomas R. Eisenreich1, and Michel C. Nussenzweig1,2

1 Laboratory of Molecular Immunology and 2 Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021
3 Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP, Illkirch, 67404 Strasbourg, France

CORRESPONDENCE Michel C. Nussenzweig: nussen{at}rockefeller.edu

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-JH 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-JH 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-JH 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-JH translocations induced by IL-6.

Abbreviations used: AID, activation-induced cytidine deaminase; IgH, Ig heavy chain; Ig V-JH, genomic region spanning the heavy chain V(D)J; RSS, recombination signal sequences; SHM, somatic hypermutation; tg, transgenic; V(D)J, variable, diversity, and joining.


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