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

  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},

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Activation-Induced Cytidine Deaminase Initiates Immunoglobulin Gene Conversion and Hypermutation by a Common Intermediate
It is shown that the stepwise removal of the ψV donors not only reduces and eventually abolishes Ig gene conversion, but also activates AID-dependent Ig hypermutation, which strongly supports a model in which AID induces a common modification in the rearranged V(D)J segment.
The complex regulation and function of activation-induced cytidine deaminase (AID)
This review discusses how AID expression and activity are regulated, including recent discoveries of AID interacting proteins that might recruit AID to immunoglobulin (Ig) genes and also allow it to target both DNA strands.
Activation-induced Deaminase (AID)-directed Hypermutation in the Immunoglobulin Sμ Region
It is reported that B cell stimulation which induces CSR but not SHM, leads to AID-dependent accumulation of SHM-like point mutations in the switch μ region, uncoupled with CSR, which strongly suggest that AID itself or a single molecule generated by RNA editing function of AID may mediate a common step ofSHM and CSR.
Activation-induced cytidine deaminase mediates central tolerance in B cells
It is demonstrated that low levels of AID in bone marrow immature and transitional B cells suppress the development of autoreactivity, and in vitro, AID deficient immature/transitional B cells are significantly more resistant to anti-IgM–induced apoptosis than their normal counterparts.
Human uracil–DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination
It is shown that recessive mutations of the gene encoding uracil–DNA glycosylase (UNG) are associated with profound impairment in CSR at a DNA precleavage step and with a partial disturbance of the SHM pattern in three patients with hyper-IgM syndrome.
Negative regulation of activation-induced cytidine deaminase in B cells.
  • T. Muto, I. Okazaki, T. Honjo
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2006
Conditional AID-transgenic mice are generated that constitutively express AID only in B cells, possibly providing an explanation for the absence of deregulation of CSR and SHM in AID -transgenic B cells.
Recombinogenic Phenotype of Human Activation-Induced Cytosine Deaminase
The initial step of base excision repair is required for AID-dependent recombination and is a branch point for either hypermutagenesis or recombination.
Activation-induced deaminase in B lymphocyte maturation and beyond.
Activation-induced deaminase (AID), a member of the AID/apolipoprotein B mRNA-editing enzyme-catalytic (APOBEC) family, deaminates DNA cytidines into uridines and is the major trans-acting player of
Controlling somatic hypermutation in immunoglobulin variable and switch regions
There is an intricate interplay between faithful DNA repair and mutagenic DNA repair during somatic hypermutation, in that some proteins from accurate repair pathways are also involved in mutagenesis.
Activation-Induced Cytidine Deaminase Does Not Impact Murine Meiotic Recombination
It is concluded that AID has a minor impact, if any, on the overall frequency of meiotic recombination, and the frequency of recombination in the female germline was greater than in male germline.


Specific Expression of Activation-induced Cytidine Deaminase (AID), a Novel Member of the RNA-editing Deaminase Family in Germinal Center B Cells*
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.
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.
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
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.
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.
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.