Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme.
Induced overexpression of AID in CH12F3-2 B lymphoma cells augmented class switching from IgM to IgA without cytokine stimulation. AID deficiency caused a complete defect in class switching and showed a hyper-IgM phenotype with enlarged germinal centers containing strongly activated B cells before or after immunization. AID-/- spleen cells stimulated in vitro with LPS and cytokines failed to undergo class switch recombination although they expressed germline transcripts. Immunization of AID-/- chimera with 4-hydroxy-3-nitrophenylacetyl (NP) chicken gamma-globulin induced neither accumulation of mutations in the NP-specific variable region gene nor class switching. These results suggest that AID may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation.
Muramatsu
M
M
Department of Medical Chemistry, Graduate School of Medicine, Institute for Virus Research, Kyoto University, Japan.
Kinoshita
K
K
Fagarasan
S
S
Yamada
S
S
Shinkai
Y
Y
Honjo
T
T
D000071479:APOBEC-1 Deaminase; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D002678:Chimera; D003564:Cytidine Deaminase / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D018095:Germ-Line Mutation / Q000187:drug effects / Q000235:genetics; D018858:Germinal Center / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D006241:Haptens / Q000494:pharmacology; D006579:Heterozygote; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000187:drug effects / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics* / Q000276:immunology; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D017393:RNA Editing; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011995:Recombination, Genetic / Q000187:drug effects / Q000235:genetics*; D013154:Spleen / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured; D005719:gamma-Globulins / Q000494:pharmacology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D016207:Cytokines; D006241:Haptens; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D005719:gamma-Globulins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase