The immune system generates diversity by using three distinct mechanisms of genetic alteration. V(D)J recombination, CSR, and SHM. Mechanistically, all three processes can be divided into at least three phases: targeting/recognition, DNA cleavage, and repair (18). In all three cases, transcription is thought to play a key role in targeting of a nuclease to the Ig locus. The cleavage step is thought to result in the production of a DNA DSB, though the creation of the DSB might not be the initial event. In V(D)J recombination for instance, the initial event is the nicking of one strand by the RAG recombinase, followed by hairpin formation and resolution into a blunt DSB (24). It is not known whether the CSR nuclease initially inflicts a single or double-strand break but there is some evidence to suggest that the final product of cleavage is a DSB (25). Finally, there is data to indicate that SHM also involves the creation of a DNA DSB, though that may not necessarily be the first step of the ...
In follicular lymphoma, somatic hypermutation of the immunoglobulin heavy chain genes facilitates the identification of different lymphoma cell clones, and the construction of genealogical trees. To analyze the dissemination of lymphoma cells, and the role of the bone marrow for disease progression, we simultaneously analyzed the somatic hypermutation patterns of lymph node and bone marrow specimens of three patients at onset and relapse. Immunoglobulin heavy chain genes were amplified by polymerase chain reaction, cloned and sequenced. Mutational pedigrees were constructed in a hierarchical order. Where direct transition of one mutation pattern into that of successor clones was not feasible, hypothetical predecessor clones were created, and a probability measurement calculation was introduced. Eighty-five sequenced clones were generated. The average mutation rates were 13,45% for the lymph nodes, and 9,78% for the bone marrows. Forty-two hypothetical predecessor clones were introduced into ...
The angiopoietin (Ang) and Tie families play an important role in the latter stages of vascular development and in adult vasculature. A variety of studies on Ang1 ligand have provided compelling evidence of its therapeutic potential and along with Ang2 plays a major role in various protective and pathological conditions. Understanding the Ang-Tie interaction by manipulation of the angiopoietins is a very desirable prospect for developing it as a protein therapeutic drug. The aim of this project was to examine the molecular basis of Ang binding using a combination of rational mutagenesis and directed evolution. Directed evolution is a powerful strategy for protein engineering. A new method of directed evolution using mammalian surface display combined with mutagenesis driven by somatic hypermutation (SHM) was investigated for engineering Ang proteins with altered binding characteristics (to Tie1 and Tie2). The Ang receptor binding domains (RBD) were cloned linked to the asialoglycoprotein ...
The CLL genome is largely devoid of the chromosomal translocations and aberrant somatic hypermutations that are involved in several B cell non-Hodgkin lymphomas (B-NHLs) (1, 2, 49, 50, 53). These observation are consistent with a post-GC or GC-independent derivation of CLL because B-NHL-associated translocations are caused by errors during somatic hypermutation and class switch recombination, two mechanisms that are active in GC B cells (23). NGS studies have further elucidated the genomic complexity of CLLs and have shown that the average number of non-silent mutations (i.e., mutations that alter the protein sequence) per case is 10-12 at diagnosis, whereas the average number of copy number abnormalities is approximately two (45, 46, 51, 52). The order of magnitude of lesions detected in the coding genome of CLL appears considerably lower than in common epithelial cancers (54). Among hematologic malignancies, the complexity of the CLL genome is also on the lower side, markedly smaller than ...
AUTHOR = {Hofmann, Wolf Peter and Fernandez, B. and Herrmann, E. and Welsch, Christoph and Mihm, Ulrike and Kronenberg, B. and Feldmann, G. and Spengler, U. and Zeuzem, Stefan and Sarrazin, Christoph ...
High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular info about humoral immunity. with antibody frequencies and somatic hypermutation to create a logistic regression model for prediction from the immunological position of clones. The model could predict clonal position with high self-confidence but only once using MAF mistake and bias PPP3CC corrected Ig-seq data. Improved accuracy by MAF supplies the potential to upfront Ig-seq and its own utility in immunology and biotechnology greatly. did not possess a precise match in the primer collection but had been still well displayed in the info set due Evacetrapib to a higher level of mispriming, suggesting that reduced primer sets may be designed that allow mismatches toward the 5 end of primers. These findings also demonstrate the need to exclude primer binding regions from full-VDJ diversity analysis, as was done throughout this study. We also investigated the role of V-geneCspecific primer annealing temperature ...
Somatic hypermutation (SHM) of immunoglobulin genes is currently viewed as a two step process initiated by the deamination of deoxycytidine (C) to
The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response.
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TY - JOUR. T1 - Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression. AU - Roa, Sergio. AU - Avdievich, Elena. AU - Peled, Jonathan U.. AU - MacCarthy, Thomas. AU - Werling, Uwe. AU - Fei, Li Kuang. AU - Kan, Rui. AU - Zhao, Chunfang. AU - Bergman, Aviv. AU - Cohen, Paula E.. AU - Edelmann, Winfried. AU - Scharff, Matthew D.. PY - 2008/10/21. Y1 - 2008/10/21. N2 - Somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes are dependent upon activation-induced cytidine deaminase (AID)-induced mutations. The scaffolding properties of proliferating cell nuclear antigen (PCNA) and ubiquitylation of its residue K164 have been suggested to play an important role organizing the error-prone repair events that contribute to the AID-induced diversification of the Ig locus. We generated knockout mice for PCNA (Pcna-/-), which were embryonic lethal. Expression of PCNA with the K164R mutation rescued the lethal ...
TY - JOUR. T1 - HSP90α deficiency does not affect immunoglobulin gene hypermutation and class switch but causes enhanced MHC class II antigen presentation. AU - Li, Yingqian. AU - Li, Shuyin. AU - Hoshino, Mari. AU - Ishikawa, Rikiya. AU - Kajiwara, Chiaki. AU - Gao, Xiang. AU - Zhao, Yaofeng. AU - Ishido, Satoshi. AU - Udono, Heiichiro. AU - Wang, Ji Yang. N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.. PY - 2012/12. Y1 - 2012/12. N2 - Heat shock protein 90 (HSP90) is a molecular chaperone required for efficient antigen presentation and cross-presentation. In addition, HSP90 was recently reported to interact with and stabilize the activation-induced cytidine deaminase (AID) and plays a critical role in immunoglobulin gene hypermutation and class switch recombination. In mice and humans, there are two HSP90 isoforms, HSP90α and HSP90β, but the in vivo role of each isoform remains largely unknown. Here we have analyzed humoral immune responses in HSP90α-deficient mice. We ...
Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID)-dependent hypermutation of Ig V(D)J rearrangements and Ig S areas, respectively, in activated B cells. in DT40 cells elevated the pace of AID-induced BMS-754807 gene conversion as much as 5-collapse. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion. Author Summary To generate highly specific antibodies in response to an immune challenge, the antibody genes in triggered B cells mutate at a very high rate over a period of several days. The enzyme that initiates antibody gene mutation is definitely activation-induced cytidine deaminase (AID), the 1st protein recognized to directly edit DNA genomes BMS-754807 in vivo. AID induces point mutation of antibody V genes in all vertebrates, as well as transfer ...
Activation-induced cytidine deaminase (AID) was discovered by Muramatsu et al. (7) as an APOBEC1 homolog with cytidine deaminase properties in stimulated B cell lines. Muramatsu et al. (8) showed that AID is necessary for somatic hypermutation and class switch recombination, because AID−/− B lymphocytes do not undergo class switch recombination and fail to accumulate mutations upon Ag stimulation. Mutations in the human AID gene causing lack of function underlie one type of hyper-IgM syndrome. In this syndrome, B cells fail to switch from IgM to other isotypes, and somatic hypermutation of the Ig V regions does not occur (9). This syndrome seemingly connects AID with Ig isotype class switch and somatic hypermutation. Arakawa et al. (10) demonstrated that AID is also required for Ig gene conversion in chicken B cell lines. Thus, AID participates in three different processes that contribute to the diversification of Abs: somatic hypermutation, isotype class switch recombination, and gene ...
Activation-induced deaminase (AID) is expressed only in germinal center B cells. There, it is required for somatic hypermutation, gene conversion and class switch recombination of antibody variable region segments, three processes that diversify antibodies during immune responses. Although AID has homology to RNA-editing enzymes, three recent reports suggest it could initiate the diversification processes by deaminating cytidine residues within the antibody genes themselves.
Activation-induced deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) by inducing mutations and double-strand breaks at the immunoglobulin (Ig) locus in B cells. AID converts deoxycytidine (dC) to deoxyuridine (dU) in single-stranded DNA (ssDNA). This deaminat …
To determine whether DNA polymerase plays a role in the hypermutation of immunoglobulin variable genes, we examined the frequency and pattern of substitutions in variable VH6 genes from the peripheral blood lymphocytes of three patients with xeroderma pigmentosum variant disease, whose polymerase had genetic defects. The frequency of mutation was normal but the types of base changes were different: there was a decrease in mutations at A and T and a concomitant rise in mutations at G and C. We propose that more than one polymerase contributes to hypermutation and that if one is absent, others compensate. The data indicate that polymerase is involved in generating errors that occur predominantly at A and T and that another polymerase(s) may preferentially generate errors opposite G and C.. ...
A significant leap forward got here in 2000 with the invention that activation-induced deaminase (AID) is actually required for hypermutation. This used to be in 2002 by means of proof that reduction without delay edits the DNA that encodes an antibody in an activated B mobile. a lot has seeing that been learnt concerning the biochemistry and rules of reduction, however the mechanism during which it truly is recruited particularly to antibody-encoding genes continues to be enigmatic. figuring out this recruitment is clinically major simply because off-target relief job at oncogenes may end up in chromosomal translocations and tumorigenesis ...
Activation-induced cytidine deaminase (AID) is essential for two processes of immunoglobulin diversification in germinal center B cells: somatic hypermutation (SHM), in which mutations are introduced into immunoglobulin (Ig) genes, and class-switch recombination (CSR), in which genomic constant regions are recombined to encode antibodies of different isotypes. Both of these processes require AID-catalyzed C-to-U lesions at the Ig loci, which are resolved to generate point mutations or double-stranded DNA breaks in the cases of SHM and CSR, respectively. Despite over a decade of intense study, a number of open issues remain surrounding AID. The diversity of findings regarding AIDs role in DNA demethylation raises the question of the scope of its involvement in this process. Additionally, while it is clear that AID-mediated damage occurs, the effects of this damage on the average B cell have not been characterized. Finally, the issue of whether AID is able to edit RNA in vivo has never been rigorously
However, we overlooked a mechanism natural has adopted for rapid evolution of proteins: adaptive immunity that generates a huge pool of antibodies.It is well-known that B-cells are capable of producing a large pool of new antibodies upon antigen stimuli, which is a most important protective mechanism for animals. People have been curious about the molecular mechanism of antibody generation. Recent works have revealed that an enzyme: Activation-Induced (Cytidine) Deaminase (AID) serves as an essential protein in three processes for antibody diversity, namely somatic hypermutation (SHM), class switch recombination (CSR) and gene conversion. Briefly speaking, AID converts cytidine to uracil by oxidizing the amino group to carbonyl group, resulting in mismatch of Watson-Crick base pair. Then DNA lesion repair pathways (base excision repair, BER; mismatch repair, MMR)are employed to bring DNA back to normal. In this process, the coding sequence for the hypervariable region of immunoglobulin is ...
Activation-induced cytidine deaminase (AICDA) antibody | Q9GZX7 | Activation-induced cytidine deaminase (AICDA), Cytidine aminohydrolase, AID
Sigma-Aldrich offers abstracts and full-text articles by [Yi Hu, Ida Ericsson, Kathrin Torseth, Stephen P Methot, Ottar Sundheim, Nina B Liabakk, Geir Slupphaug, Javier M Di Noia, Hans E Krokan, Bodil Kavli].
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Prof. McGuigan from Cardiff School of Pharmacy, UK along with Prof. Jan Balzarini of Rega Instutute for Medical Research, Belgium have reported an innovative approach to overcome the cancer Resistance mechanism using the pro-tide technology of theirs. They prepared various Nucleotide Phosphoramidates of the known anticancer drug Gemcitabine and were able to find a molecule that was resistant to cytidine deaminase-mediated […]. » Read more ...
Project details This project will use novel genetic approaches to study the role of hypermutation in the development of bladder cancer. Cytidine deaminases from the APOBEC-family make a major contribution to the mutational landscape of cancers from the bladder, the breast and the lung.
article{5d2077f0-1ddb-4387-bedd-5d50b87c515f, abstract = {,p,Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest ...
B lymphocytes respond to Ags through engagement of the BCR by direct binding to the mIg. As a consequence, depending on the differentiation status of the B cells, the strength and duration of the interaction, presence or absence of costimulatory or inhibitory signals, cells are induced to proliferate and differentiate into plasma cells, or anergy or apoptosis is induced (28). In particular, mature B cells and memory B cells switched to IgA, IgG or IgE isotypes are recruited into germinal centers, where active somatic hypermutation leading to affinity maturation takes place. In this process, a large number of cells also fail to successfully engage Ag and die by apoptosis (15). The mechanism by which the BCR delivers apoptotic signaling is far from being clear (29, 30). Different regulation of BCR signaling through the B cell coreceptor CD22 was reported to be dependent on the distinct cytoplasmic tails (μ and γ) of the mIg isotypes (31). Also, for the ε-isotype, signal transduction was ...
Why are some B-cell lineages more abundant than others, and why are some epitopes targeted more often? This is known as the problem of immunodominance-the preferential targeting by the immune system of certain antigenic sites over others (ch. 6 of [115]), and its importance was recognized long before the development of modern methods of repertoire profiling (e.g. [116-118]). Differences in immunodominance may explain variation in susceptibility between people to the same pathogen. But how does it arise?. Repertoire diversity in the first exposure to antigen is regulated by opposing forces of poorly known strength. Affinity maturation acts on only a subset of the naive repertoire, but from this initial pool, somatic hypermutation introduces mutations that increase genetic and phenotypic variation (phenotype here refers to the affinity and specificity of B cells to various epitopes). Strong competition between B cells for both antigen and T cell help inside germinal centres discards many mutations ...
TY - JOUR. T1 - Comparable impact of mutational and selective influences in shaping the expressed repertoire of peripheral IgM+/CD5- and IgM+/CD5+ B cells. AU - Dörner, Thomas. AU - Brezinschek, Hans Peter. AU - Foster, Sandra J.. AU - Brezinschek, Ruth I.. AU - Farner, Nancy L.. AU - Lipsky, Peter E.. PY - 1998/2. Y1 - 1998/2. N2 - Somatic hypermutation and subsequent selection play a significant role in shaping the peripheral B cell repertoire. This repertoire is composed of CD5+ (5%) and CD5- B cells (95%) which are known to traffic through different lymphoid compartments. Previous studies have shown that V(H) gene usage by CD5+ and CD5- B cells is similar, although mutations are more frequent in the latter. However, the effect of mutation and subsequent selection on the expressed V(H) repertoire of CD5+ and CD5- B cells has not been delineated in detail. This study, therefore, analyzed the mutational pattern of individual IgM+/CD5+ and IgM+/CD5- B cells. In both populations, mutations can ...
1YXT: Crystal structures of proto-oncogene kinase Pim1: a target of aberrant somatic hypermutations in diffuse large cell lymphoma.
1YXS: Crystal structures of proto-oncogene kinase Pim1: a target of aberrant somatic hypermutations in diffuse large cell lymphoma.
The Taft-Hartley Act made major changes to the Wagner Act. Although Section 7 was retained intact in the revised law, new language was added to provide that employees had the right to refrain from participating in union or mutual aid activities except that they could be required to become members in a union as a condition of employment.
Quantitative RT-PCR analysis of activation-induced cytidine deaminase expression in tissue samples from mantle cell lymphoma and B-cell chronic lymphocytic leukemia patients ...
Definition of activation-induced cytidine deaminase. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.
By creating an extremely diverse antibody repertoire, B cells protect the body against numerous infectious pathogens. Generation of this antibody repertoire depends on immunoglobulin gene modification events driven by four different molecular processes: V(D)J recombination, somatic hypermutation, class switch recombination, and gene conversion. The enzyme AID (activation-induced cytidine deaminase) is known to be involved in somatic hypermutation and class switch recombination. In their Perspective, Fugmann and Schatz explain that AID is also essential for gene conversion ( Arakawa et al.) and discuss how AID could operate in these three quite different processes. ...
Induced overexpression of AID in CH12F3-2 B lymphoma cells augmented class switching from IgM to IgA without cytokine stimulation. AID deficiency caused a complete defect in class switching and showed a hyper-IgM phenotype with enlarged germinal centers containing strongly activated B cells before o …
Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation. The phosphatidylinositol 3-kinase δ (PI3Kδ) pathway regulates AID by suppressing its expression in B cells. Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kδ activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells. Here we show that treatment of primary mouse B cells with idelalisib or duvelisib, and to a lesser extent ibrutinib, enhanced the expression of AID and increased ...
Deoxyuridine (dU) is a pyrimidine deoxyribonucleoside, and a derivative of the nucleoside uridine, with the only difference being that, in dU, a hydrogen (-H) group is substituted for uridine s OH group located at the 2 -position of the ribose. dU is generated in cellular DNA as a deamination product of dC (deoxycytidine), with the deamination process catalyzed by the enzyme AID (activation-induced cytidine deaminase) (1). AID is a B cell-specific gene that is necessary for antibody gene diversification via class-switch recombination and somatic hypermutation (2, 3). The dC-to-dU conversion(s) by AID occurs in the IgG locus, with various gene diversification pathways arising from the different DNA repair mechanisms used by B-cells to repair the dU lesion (1).. dC-to-dU conversion via cytidine deamination is also implicated in innate immunity to retroviruses. Here deamination of dC is mediated by the enzyme APOBEC3G, which is present in T cells, acting on the first (minus) strand cDNA of ...
To address the physiological significance of AID phosphorylation at Ser38, analysis of a mouse model (in which AIDS38A is expressed at physiological levels utilizing its endogenous control elements) was required. Two recent studies reported the generation and analysis of mice expressing only the AIDS38A mutant protein, which occurred at levels quite comparable with those of wild-type mAID expression in activated B-cells, from their endogenous AID alleles [45,51]. In addition, one of these studies also demonstrated that the AIDS38A protein expressed from the endogenous AID allele failed to associate with RPA in vivo [51]. Both studies found that mice homozygous for the AIDS38A (AIDS38A/S38A) mutation have quite severe CSR defects, demonstrating clearly that the apparently normal levels of CSR reported for this mutant form of AID by others [49] probably resulted from overexpression of the mutant protein as proposed in [47].. Activation of AIDS38A/S38A B-cells with αCD40 and IL-4 (interleukin 4) ...
Our system to produce antibodies is critical for our survival against numerous infections, but it causes also many tumors. B-lymphocytes can modify their immunoglobulin (Ig) genes to generate specific antibodies with a new isotype and enhanced affinity against an antigen. Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates these processes by deaminating cytosine to uracil. How somatic hypermutation (SH) and class switch recombination (CSR) are targeted is key to understanding the defect DNA integrity in lymphomas and also in other tumors where inflammatory signals aberrantly induces AID. The trans-acting factors mediating specific targeting of AID and thereby SH and CSR have remained elusive. Here we show that mutant E2A with defect inhibition by the Ca2+sensor protein calmodulin results in reduced B cell receptor- (BCR-), IL4-plus CD40 ligand-stimulated CSR to IgE and instead aberrant CSR. AID is shown to be together with the transcription factors E2A, ...
The primary finding of this study was the emergence of a distinct A-to-G/U-to-C hypermutation pattern in the single-stranded RNA genome of LCMV both in cell culture and in the organs of infected mice. This pattern is probably due to unspecific deamination by ADAR1-L, which was found to be upregulated during infection of cells and mice with LCMV. Furthermore, these A-to-G mutations lead to a high percentage of nonfunctional viral protein, thereby weakening viral fitness.. The A-to-G hypermutation pattern observed in this study was most likely attributed to RNA editing and not to errors of the viral polymerase. The hypermutation pattern was not observed 2 days after infection in L929 cells. In mice at days 5 and 8 p.i., the dominance of A-to-G mutations is also reduced compared to that at day 4, which is consistent with lower ADAR1-L expression at these time points. Furthermore, although viral RNA polymerases lack 3′-to-5′ proofreading activity, they have never been reported to exhibit a ...
Several lines of work suggest that the 3′ enhancer region would control CSR. Chromatin interactions between heavy chain genes and HS1,2 suggest functional interactions (Wuerffel et al., 2007). Deletions or replacements of individual hypersensitive regions (Cogné et al., 1994; Manis et al., 1998; Seidl et al., 1999) implicate the 3′ regulatory locus in CSR. Additionally, insertions of foreign sequence in the locus also affect CSR, possibly by disrupting interactions between enhancer elements (Seidl et al., 1999). However, any conclusions are complicated by the fact that clean deletion of single elements reveals only a minimal phenotype (Manis et al., 1998; Seidl et al., 1999; Vincent-Fabert et al., 2009). Deletion of both HS3B and HS4 (Pinaud et al., 2001) from the germline demonstrates a role in CSR to some heavy chain genes. To pursue the role of the 3′ enhancer region, over the last 10 yr, several laboratories have attempted to delete all four elements from the mouse germline, but for ...
From the host immune perspective, the generation of genomic diversity is used as both a defensive and an offensive weapon. Host mutator enzymes such as Activation-Induced Cytidine Deaminase (AID) seed diversity in the adaptive immune system by introducing targeted mutations into the immunoglobulin locus that result in antibody maturation. Related deaminases of the innate immune system can directly attack retroviral threats by garbling the pathogen genome through mutation, as accomplished by the deaminase APOBEC3G, which restricts infection with HIV. Immune mutator enzymes, however, also pose a risk to the host, as overexpression or dysregulation have been associated with oncogenesis ...
Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here we demonstrated that TNF-α stimulation induced transcriptional downregulation of MSH2, a member of the mismatch repair family, via nuclear factor-κB-dependent miR-21 expression in hepatocytes. Liver cancers developed in ALB-MSH2-/-AID+, ALB-MSH2-/-, and ALB-AID+ mice in which MSH2 is deficient and/or activation-induced cytidine deaminase (AICDA) is expressed in cells with albumin-producing hepatocytes. The mutation signatures in the tumors developed in these models, especially ALB-MSH2-/-AID+ mice, closely resembled those of human hepatocellular carcinoma. Our findings demonstrated that inflammation-mediated dysregulation of MSH2 may be a mechanism of genetic alterations during hepatocarcinogenesis. ...
Gene conversion-like events between rearranged IGHV3-23*01 gene sequences and germline VH sequences superimposed by somatic hypermutation (SHM). IGHV3-23*01 mut
This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008 ...
Results TNF blockade augmented B cell activation as reflected by the expression of early activation markers, CD40, and costimulatory molecules, without affecting differentiation towards plasmablasts. This was associated with a specific increase of the unswitched fraction of circulating memory B cells and a decreased level of somatic hypermutation in anti-TNF treated patients, indicating an impairment of the germinal centre-dependent B cell maturation. In agreement with these findings, TNF blockade profoundly suppressed the response to the TD vaccination against hepatitis B, whereas the T cell-independent response against pneumococcal polysaccharides was only modestly affected.. ...
The effects of somatic hypermutation on neutralization and binding in the PGT121 family of broadly neutralizing HIV antibodies. Devin Sok*, Uri Laserson*, Jonathan Laserson*, Yi Liu*, Francois Vigneault, Jean-Philippe Julien, Bryan Briney, Alejandra Ramos, Karen F Saye, Khoa Le, Alison Mahan, Shenshen Wang, Mehran Kardar, Gur Yaari, Laura M Walker, Birgitte B Simen, Elizabeth P St John, Po-Ying Chan-Hui, Kristine Swiderek, Stephen H Kleinstein, Galit Alter, Michael S Seaman, Arup K Chakraborty, Daphne Koller, Ian A Wilson, George M Church, Dennis R Burton, Pascal Poignard. PLoS Pathogens 2013. doi:10.1371/journal.ppat.1003754 , pdf. ...
Centers for Disease Control and Prevention - To develop and implement HIV prevention programs of public information and education ...
1yxu: Crystal structures of proto-oncogene kinase Pim1: a target of aberrant somatic hypermutations in diffuse large cell lymphoma.
To protect the genome from serious, potentially oncogenic effects associated with off-target mutations, both AID activity and mutagenic repair are targeted specifically to your Ig genes. A potential player in this process is the DNA-damage-sensing enzyme PARP-1, which recruits DNA … Continue reading →. ...