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
|
Resource |
DNA material |
pAID-GTOP (RDB03000)
pmAID BSSK (RDB02864). |