Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme

@article{Muramatsu2000ClassSR,
  title={Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme},
  author={Masamichi Muramatsu and Kazuo Kinoshita and Sidonia Fagarasan and Shu-ichi Yamada and Yoichi Shinkai and Tasuku Honjo},
  journal={Cell},
  year={2000},
  volume={102},
  pages={553-563}
}

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    Proceedings of the National Academy of Sciences of the United States of America
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Activation-Induced Cytidine Deaminase Does Not Impact Murine Meiotic Recombination
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References

SHOWING 1-10 OF 165 REFERENCES
Specific Expression of Activation-induced Cytidine Deaminase (AID), a Novel Member of the RNA-editing Deaminase Family in Germinal Center B Cells*
TLDR
Findings suggest that AID is a new member of the RNA-editing deaminase family and may play a role in genetic events in the germinal center B cell.
Efficient recombination of a switch substrate retrovector in CD40-activated B lymphocytes: implications for the control of CH gene switch recombination.
TLDR
It is shown that cultures of purified murine and human B cells, stimulated only by CD40 receptor engagement, possess a potent switch recombinations activity and the efficiency of switch recombination with SSRs resembles that seen for endogenous C(H) class switching.
High frequency class switching of an IgM+ B lymphoma clone CH12F3 to IgA+ cells.
TLDR
It is found that the extents of methylation and the amounts of germline transcripts do not necessarily correlate with the efficiency of recombination in induced CH12F3 cells, leading to the proposal that switch recombination can be separated into at least two phases.
Shutdown of class switch recombination by deletion of a switch region control element
TLDR
Recombination to a particular switch region was abolished in mice that were altered to lack sequences that are 5' to the s gamma 1 region, which directly implicates the functional importance of 5' switch region flanking sequences in the control of class switch recombination.
Isolation, tissue distribution, and chromosomal localization of the human activation-induced cytidine deaminase (AID) gene.
TLDR
The gene encoding activation-induced cytidine deaminase (AID) was isolated from a murine B cell lymphoma line, CH12F3-2, induced by combined stimulation of TGF-beta, IL-4, and CD40L and RT-PCR analysis of 15 human tissues showed that AID mRNA is expressed strongly in lymph nodes and tonsils.
Specificity of immunoglobulin heavy chain switch correlates with activity of germline heavy chain genes prior to switching.
TLDR
Results suggest that I.29 cells switch specifically to IgA, IgE or IgG2a due to the activation of the corresponding H chain constant region genes in IgM+ cells prior to the actual switch recombination event.
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