Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice

doi:10.1073/pnas.0610732104

Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice

Departments of *Immunology and Genomic Medicine and of
^‡Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida Konoe-Cho, Sakyo-Ku, Kyoto 606-8501, Japan;
^†Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Enya-Cho 89-1, Izumo City, Shimane 693-8501, Japan; and
^§Evolutionary Medicine, Shiga Medical Institute, 5-4-30, Moriyama, Shiga 524-8524, Japan

Contributed by Tasuku Honjo, December 6, 2006 (received for review November 9, 2006)

Abstract

Activation-induced cytidine deaminase (AID), which is essential to both class switch recombination and somatic hypermutation of the Ig gene, is expressed in many types of human B cell lymphoma/leukemia. AID is a potent mutator because it is involved in DNA breakage not only of Ig but also of other genes, including proto-oncogenes. Recent studies suggest that AID is required for chromosomal translocation involving cmyc and Ig loci. However, it is unclear whether AID plays other roles in tumorigenesis. We examined the effect of AID deficiency on the generation of surface Ig-positive B cell lymphomas in Emu-cmyc transgenic mice. Almost all lymphomas that developed in AID-deficient transgenic mice were pre-B cell lymphomas, whereas control transgenic mice had predominantly B cell lymphomas, indicating that AID is required for development of B but not pre-B cell lymphomas from cmyc overexpressing tumor progenitors. Thus, AID may play multiple roles in B cell lymphomagenesis.

Footnotes

^¶To whom correspondence should be addressed. E-mail: honjo{at}mfour.med.kyoto-u.ac.jp
Author contributions: A.K. and T.H. designed research; A.K., N.K., T.T., and I.-m.O. performed research; M.M., K.K., H.N., and D.Y. contributed new reagents/analytic tools; A.K., N.K., and T.T. analyzed data; and A.K. and T.H. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0610732104/DC1.
Abbreviations:

AID,

activation-induced cytidine deaminase;

SHM,

somatic hypermutation;

CSR,

class switch recombination;

GC,

germinal center;

Tg,

transgenic.