Mini‐review Activation‐induced cytidine deaminase: a dual role in class‐switch recombination and somatic hypermutation

@article{Durandy2003MinireviewAC,
  title={Mini‐review Activation‐induced cytidine deaminase: a dual role in class‐switch recombination and somatic hypermutation},
  author={Anne Durandy},
  journal={European Journal of Immunology},
  year={2003},
  volume={33}
}
  • A. Durandy
  • Published 1 August 2003
  • Biology, Medicine
  • European Journal of Immunology
Maturation of the antibody repertoire is mediated by two different mechanisms: class‐switch recombination (CSR) and somatic hypermutation (SHM). These two processes are T cell dependent and occur in the germinal centers of secondary lymphoid organs. CSR leads to the production of antibodies of different isotypes whereas SHM leads to the selection of B cells expressing a BCR with high affinity for antigen. The activation‐induced cytidine deaminase (AID) was recently shown to play a key role in… 
Characterization of a new V gene replacement in the absence of activation‐induced cytidine deaminase and its contribution to human B‐cell receptor diversity
TLDR
It is reported that human B cells can, surprisingly, undergo type 2 replacement associated with κ light‐chain rearrangements, and this unusual mechanism of homologous recombination seems to be a variant of gene conversion‐like recombination, which does not require AID.
Preventing AID, a physiological mutator, from deleterious activation: regulation of the genomic instability that is associated with antibody diversity.
TLDR
This review summarizes the recently elucidated comprehensive transcriptional regulation mechanisms of the AID gene and the post-transcriptional regulation that may be critical for preventing excess AID activity and discusses why AID targets not only Igs but also other proto-oncogenes.
Molecular Analysis of Activation-Induced Cytidine Deaminase Gene in Immunoglobulin-E Deficient Patients
TLDR
Conformational sensitive gel electrophoresis and sequencing analysis of AICDA coding sequences demonstrated sequence heterogeneity due to 5923A/G and 7888C/T polymorphisms, but did not reveal any novel mutation that might explain the selective IgE deficit.
Identification of a Specific Domain Required for Dimerization of Activation-induced Cytidine Deaminase*
TLDR
It is demonstrated that AID molecules form a homodimer autonomously in the absence of RNA, DNA, other cofactors, or post-translational modifications.
Characterizing RNF20 and RNF40 in the Class Switching of B Cells
TLDR
If the hypothesis is correct, RNF20 and RNF40 will be discovered to be critical factors in the CSR process in B cells, and therefore in establishing an effective antibody response that is critical in protective immunity.
The Double-Edged Sword of Activation-Induced Cytidine Deaminase1
TLDR
It is shown that AID associates with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) promoting cell survival, presumably by resolving DNA double-strand breaks, resolving the paradox of how B cells undergoing DNA cytidine deamination and recombination exhibit heightened survival.
No Overt Clinical Immunodeficiency Despite Immune Biological Abnormalities in Patients With Constitutional Mismatch Repair Deficiency
TLDR
Neither clinical nor routine immunological laboratory parameters were consistently suggestive of PID in these CMMRD patients, but previously shown abnormalities in SHM and rearranged heavy chain transcripts were confirmed.
Activation-Induced Cytidine Deaminase Expression in Follicular Dendritic Cell Networks and Interfollicular Large B Cells Supports Functionality of Ectopic Lymphoid Neogenesis in Autoimmune Sialoadenitis and MALT Lymphoma in Sjögren’s Syndrome1
TLDR
It is reported that AID retains its exclusive association with numerous, residual GCs in parotid SS-MALT lymphomas, whereas neoplastic marginal zone-like B cells are consistently AID negative, which strongly support the notion that ectopic lymphoid structures in SS-SGs express the molecular machinery to support local autoantibody production and B cell expansion and may play a crucial role toward lymphomagenesis.
Response to Comment on “Activation-Induced Cytidine Deaminase Expression in Follicular Dendritic Cell Networks and Interfollicular Large B Cells Supports Functionality of Ectopic Lymphoid Neogenesis in Autoimmune Sialoadenitis and MALT Lymphoma in Sjögren’s Syndrome”
key enzyme triggering class switch recombination (CSR) and somatic hypermutation (SHM) (3), these results strongly support that a local selection and proliferation of reactive B cells take place
CpG Drives Human Transitional B Cells to Terminal Differentiation and Production of Natural Antibodies
TLDR
The ability of transitional B cells to sense bacterial DNA through TLR9 represents a tool to rapidly build up the repertoire of natural Abs necessary for the first-line defense at birth, as well as proving that IgM memory is the B cell compartment responsible for the defense against encapsulated bacteria.
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TLDR
It is concluded that transcription targets the DNA deamination activity of AID to dsDNA by generating secondary structures that provide ssDNA substrates that provide double-stranded substrates in vitro.
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TLDR
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 mu region, uncoupled with CSR.
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TLDR
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.
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TLDR
Results suggest that AID may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation in CH12F3-2 B lymphoma.
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TLDR
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TLDR
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TLDR
Class switch recombination and somatic hypermutation have been considered to be mediated by different molecular mechanisms, but involvement of activation-induced cytidine deaminase in both CSR and SHM has revealed that the two genetic alteration mechanisms are surprisingly similar.
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TLDR
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TLDR
The results provide strong support for the DNA deamination model for antibody diversification with respect to class-switching as well as hypermutation and suggest that UNG is the major mouse DNA glycosylase responsible for processing the programmed dU/dG lesions within the immunoglobulin locus.
De novo protein synthesis is required for the activation-induced cytidine deaminase function in class-switch recombination
TLDR
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