Negative regulation of activation-induced cytidine deaminase in B cells.
Both class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig genes require the activity of activation-induced cytidine deaminase (AID). Expression of AID is restricted to B cells in the germinal centers of the lymphoid organs, where activated B cells undergo CSR and SHM. We previously showed that constitutive and systemic expression of AID leads to tumorigenesis in T cells and lung epithelium, but not in B cells. This finding led us to suspect that transgenic AID may be inactivated at least in part in B cells. To address this issue, we generated conditional AID-transgenic mice that constitutively express AID only in B cells. Studies on the cross between the AID-transgenic and AID-deficient mice showed that abundant AID protein accumulated by constitutive expression is inactivated in B cells, possibly providing an explanation for the absence of deregulation of CSR and SHM in AID-transgenic B cells.
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Taro
T
Muto
Il-mi
IM
Okazaki
Shuichi
S
Yamada
Yoshimasa
Y
Tanaka
Kazuo
K
Kinoshita
Masamichi
M
Muramatsu
Hitoshi
H
Nagaoka
Tasuku
T
Honjo
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase