RRC ID 50599
Author Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T.
Title Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme.
Journal Cell
Abstract 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.
Volume 102(5)
Pages 553-63
Published 2000-9-1
DOI 10.1016/s0092-8674(00)00078-7
PII S0092-8674(00)00078-7
PMID 11007474
MeSH APOBEC-1 Deaminase Animals B-Lymphocytes / drug effects B-Lymphocytes / enzymology B-Lymphocytes / immunology B-Lymphocytes / pathology Chimera Cytidine Deaminase / deficiency Cytidine Deaminase / drug effects Cytidine Deaminase / genetics Cytidine Deaminase / metabolism* Cytokines / pharmacology Enzyme Induction Female Flow Cytometry Gene Deletion Germ-Line Mutation / drug effects Germ-Line Mutation / genetics Germinal Center / drug effects Germinal Center / enzymology Germinal Center / immunology Germinal Center / pathology Haptens / pharmacology Heterozygote Immunoglobulin A / genetics Immunoglobulin A / immunology Immunoglobulin Class Switching / drug effects Immunoglobulin Class Switching / genetics* Immunoglobulin M / genetics* Immunoglobulin M / immunology Immunohistochemistry Lipopolysaccharides / pharmacology Lymphocyte Activation / drug effects Male Mice Mice, Knockout Mutation / drug effects Mutation / genetics* RNA Editing* RNA, Messenger / analysis RNA, Messenger / genetics Recombination, Genetic / drug effects Recombination, Genetic / genetics* Spleen / drug effects Spleen / enzymology Spleen / immunology Spleen / pathology Tumor Cells, Cultured gamma-Globulins / pharmacology
IF 38.637
Times Cited 2305
DNA material pAID-GTOP (RDB03000) pmAID BSSK (RDB02864).