Disease relevance of Aicda

• A role for activation-induced cytidine deaminase in the host response against a transforming retrovirus [1].
• To elucidate the role of class switch recombination (CSR) and somatic hypermutation (SHM) in virus infection, we have investigated the influence of the primary and secondary infections of influenza virus on mice deficient of activation-induced cytidine deaminase (AID), which is absolutely required for CSR and SHM [2].
• Activation-induced cytidine deaminase (AID), which is essential to both class switch recombination and somatic hypermutation of the Ig gene, is expressed in many types of human B cell lymphoma/leukemia [3].
• The Wiskott-Aldrich syndrome protein (WASP) family activates the Arp2/3 complex leading to the formation of new actin filaments [4].

High impact information on Aicda

• Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme [5].
• Activation-induced cytidine deaminase (AID), which is specific to B lymphocytes, is required for class switch recombination (CSR)--a process mediating isotype switching of immunoglobulin--and somatic hypermutation--the introduction of many point mutations into the immunoglobulin variable region genes [6].
• Activation-induced cytidine deaminase (AID), a putative RNA-editing cytidine deaminase, is expressed strictly in activated B cells and is indispensable in both CSR and somatic hypermutation [7].
• V(D)J recombination proceeds via precise DNA cleavage initiated by the RAG proteins at short conserved signal sequences, whereas CSR and SHM are initiated over large target regions via activation-induced cytidine deaminase (AID)-mediated DNA deamination of transcribed target DNA [8].
• Activation-induced cytidine deaminase (AID) is specifically expressed in the germinal centers of lymphoid organs, where it initiates targeted hypermutation of variable regions of immunoglobulin genes in response to stimulation by antigen [1].

Biological context of Aicda

• Taken together, our observations link helix-loop-helix activity and Aicda gene expression in a common pathway, in which E-protein activity is required for the efficient induction of Aicda transcription [9].
• Our studies show that impaired induction of E47, and subsequently activation-induced cytidine deaminase, contribute to poor CSR and production of secondary isotypes in senescence [10].
• Somatic hypermutation and class switch recombination of immunoglobulin genes are dependent on the presence of the activation-induced cytidine deaminase (AICDA) enzyme [11].
• Activation-induced cytidine deaminase (AID) is a 'master molecule' in immunoglobulin (Ig) class-switch recombination (CSR) and somatic hypermutation (SHM) generation, AID deficiencies are associated with hyper-IgM phenotypes in humans and mice [12].
• Antibody diversification by somatic hypermutation, gene conversion, and class switch recombination is completely dependent on activation-induced cytidine deaminase (AID) [13].

Anatomical context of Aicda

• Here we show that activated B cells overexpressing the antagonist helix-loop-helix protein Id3 do not induce expression of the murine Aicda gene encoding activation-induced deaminase (AID) [9].
• Activation-induced cytidine deaminase (AID) is shown to be essential and sufficient to induce both CSR and SHM in artificial substrates in fibroblasts as well as B cells [14].
• These cells carried few Ig somatic mutations, expressed germ-line Cgamma1- and activation-induced cytidine deaminase-specific transcripts and likely include GC B cell founders and/or plasma cell precursors [15].
• Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells [16].
• However, one unusually large lymph node tumor expressed a high level of Aid constitutively [17].

Associations of Aicda with chemical compounds

• Key intermediates in somatic hypermutation are deoxyuridine lesions, introduced by activation-induced cytidine deaminase [18].
• RNA-editing hypothesis postulates that activation-induced cytidine deaminase deaminates cytosine in an unknown mRNA to generate a new mRNA encoding an endonuclease for CSR and thus predicts that DNA cleavage depends on de novo protein synthesis [19].
• DNA deaminases of the Aid/Apobec family convert cytosine into uracil and play key roles in acquired and innate immunity [20].
• Here we show that Aid and Apobec1 are 5-methylcytosine deaminases resulting in a thymine base opposite a guanine [20].
• Both SHM and CSR are initiated by activation-induced cytidine deaminase (AID), which deaminates deoxycytidine to deoxyuridine in single-stranded DNA (ssDNA) [21].

Other interactions of Aicda

• In this study, we examined the activation of Stat5 and activation-induced cytidine deaminase (AID) in CD38-activated murine splenic B cells by IL-5 [22].
• To determine whether Mbd4 functions downstream of activation-induced cytidine deaminase activity, we examined somatic hypermutation and CSR in Mbd4(-/-) mice [23].
• Activation-induced cytidine deaminase (AID) is indispensable for immunoglobulin maturation by somatic hypermutations and class switch recombination and is supposed to deaminate cytidines in DNA, while its homolog APOBEC-1 edits apolipoprotein (apo) B mRNA by cytidine deamination [24].
• This suggests that Msh2 may play a role in repairing activation-induced cytidine deaminase-generated G-U mismatches [25].
• Ongoing isotype switching was found in both normal and microMT B cell development as reflected by detection of IgG1 germline and postswitch transcripts as well as activation-induced cytidine deaminase expression, resulting in the generation of IgG-expressing cells [26].

Analytical, diagnostic and therapeutic context of Aicda

• Several tumors as well as controls only expressed detectable amounts of the Aid deaminase after mitogenic stimulation, as estimated by real-time PCR of transcripts [17].
• Sequence analysis of the I mu -- C mu intron in in vitro activated-mutant splenocytes did not reveal any significant increase in activation-induced cytidine deaminase (AID)-induced somatic mutations [27].
• Finally, using Northern blot analysis we show that the activation-induced cytidine deaminase, an essential trans-factor for the in vivo hypermutation mechanism, is transcribed in the hypermutating cell line 18-81 [28].

References