Activation-induced deaminase (AID)-directed hypermutation in the immunoglobulin Smu region: implication of AID involvement in a common step of class switch recombination and somatic hypermutation.
Somatic hypermutation (SHM) and class switch recombination (CSR) cause distinct genetic alterations at different regions of immunoglobulin genes in B lymphocytes: point mutations in variable regions and large deletions in S regions, respectively. Yet both depend on activation-induced deaminase (AID), the function of which in the two reactions has been an enigma. Here we report that B cell stimulation which induces CSR but not SHM, leads to AID-dependent accumulation of SHM-like point mutations in the switch mu region, uncoupled with CSR. These findings strongly suggest that AID itself or a single molecule generated by RNA editing function of AID may mediate a common step of SHM and CSR, which is likely to be involved in DNA cleavage.
Nagaoka
Hitoshi
H
Department of Medical Chemistry Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-Ku, Kyoto 606-8501, Japan.
Muramatsu
Masamichi
M
Yamamura
Namiko
N
Kinoshita
Kazuo
K
Honjo
Tasuku
T
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D017353:Gene Deletion; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D017393:RNA Editing; D011995:Recombination, Genetic / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007075:Immunoglobulin M; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase