IL-4-induced AID expression and its relevance to IgA class switch recombination.
Activation-induced cytidine deaminase (AID) is an inducible gene that plays a critical role in Ig class switch recombination and somatic hypermutation in B cells. We explored the mechanisms by which IL-4 induces AID expression in mouse B cells. IL-4 increased AID expression and over-expression of Stat6 further augmented IL-4-induced promoter activity. The involvement of Stat6 in the promoter activity was confirmed using ChIP assays and site-directed mutagenesis. Treatment with H89, a PKA inhibitor, markedly decreased IL-4-induced AID expression, and over-expression of CREB enhanced it. These results indicate that Stat6 and PKA/CREB are involved in IL-4-induced AID expression. The relevance of these signal transducing molecules was verified using the TGFbeta1-induced IgA isotype switching model. Our results indicate that IL-4, through Stat6 and PKA/CREB, induces AID expression leading to Ig isotype switching event.
Kim
Ran Ju
RJ
Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chunchon 200-701, Republic of Korea.
Kim
Hyun-A
HA
Park
Jae-Bong
JB
Park
Seok-Rae
SR
Jeon
Seong-Hyun
SH
Seo
Goo-Young
GY
Seo
Dong-Wan
DW
Seo
Su Ryeon
SR
Chun
Gie-Taek
GT
Kim
Nam-Soo
NS
Yie
Se-Won
SW
Byeon
Woo-Hyeon
WH
Kim
Pyeung-Hyeun
PH
D000818:Animals; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D007070:Immunoglobulin A / Q000235:genetics*; D017578:Immunoglobulin Class Switching / Q000187:drug effects / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D018448:Models, Immunological; D011401:Promoter Regions, Genetic / Q000235:genetics; D011995:Recombination, Genetic / Q000187:drug effects / Q000235:genetics*; D050800:STAT6 Transcription Factor / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D017362:Cyclic AMP Response Element-Binding Protein; D007070:Immunoglobulin A; D050800:STAT6 Transcription Factor; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase