AID mutant analyses indicate requirement for class-switch-specific cofactors.
Activation-induced cytidine deaminase (AID) is the essential and sole B cell-specific factor required for class-switch recombination (CSR) and somatic hypermutation (SHM). However, it is not known how AID differentially regulates these two independent events. Involvement of several cofactors interacting with AID has been indicated by scattered distribution of loss-of-function point mutations and evolutionary conservation of the entire 198-amino-acid protein. Here, we report that human AID mutant proteins with insertions, replacements or truncations in the C-terminal region retained strong SHM activity but almost completely lost CSR activity. These results indicate that AID requires interaction with a cofactor(s) specific to CSR.
Ta
Van-Thanh
VT
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan.
Nagaoka
Hitoshi
H
Catalan
Nadia
N
Durandy
Anne
A
Fischer
Alain
A
Imai
Kohsuke
K
Nonoyama
Shigeaki
S
Tashiro
Junko
J
Ikegawa
Masaya
M
Ito
Satomi
S
Kinoshita
Kazuo
K
Muramatsu
Masamichi
M
Honjo
Tasuku
T
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007105:Immune Complex Diseases / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007134:Immunoglobulin Switch Region / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000276:immunology; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology*; D014162:Transfection
D007075:Immunoglobulin M; D011994:Recombinant Proteins; D004247:DNA; D003564:Cytidine Deaminase