2.Activation-induced cytidine deaminase (AID) involved in the regulation of B cell immune senescence.
Jiaping XIAO ; Jun LI ; Xinsheng YAO
Chinese Journal of Cellular and Molecular Immunology 2023;39(5):474-478
The humoral immune response of B cells is the key to the protection of specific immunity, and immune aging reshapes its production and function. The decreased B cell immune function is an indicator of immune senescence. The impaired humoral immune function mediated by antibody secreted by B cells leads to a decline in the response of elderly individuals to the vaccine. These people are therefore more susceptible to infection and deterioration, and have a higher incidence of tumors and metabolic diseases. Activation-induced cytidine deaminase (AID) is an enzyme that triggers immunoglobulin class conversion recombination (CSR) and somatic high frequency mutation (SHM). It decreases during immune senescence and is considered to be a biomarker of decreased B cell function in aging mice and humans. Understanding the inherent defects of B-cell immune senescence and the regulation mechanism of AID in the aging process can provide new research ideas for the susceptibility, prevention and treatment of diseases in the elderly.
Animals
;
Humans
;
Mice
;
Aging/metabolism*
;
B-Lymphocytes/metabolism*
;
Cytidine Deaminase/metabolism*
;
Somatic Hypermutation, Immunoglobulin
3.Enhanced protein production of Vif and APOBEC3G by HIV-1 Vpr.
Lin LI ; Dong LIANG ; Jing-yun LI ; Yu-qi ZHAO
Chinese Journal of Experimental and Clinical Virology 2008;22(1):39-41
OBJECTIVEGoal of this study was to test the potential regulatory effects of Vpr on Vif and Vif-mediated degradation of APOBEC3G.
METHODSThe Vpr effect was first tested in a fission yeast RE007 strain that carries a single integrated copy of vpr gene in the chromosome and transformed with a vif-expressing plasmid. Similar tests were also carried out in a muristerone A vpr-inducing HEK293 mammalian cell line that were transfected with the plasmids expressing vif and/or APOBEC3G. Western Blot analyses were used to measure the corresponding protein levels under different experimental conditions.
RESULTSExpression of HIV-1 vpr appears to enhance the protein levels of Vif both in fission yeast and mammalian cells. A similar enhancement effect of APOBEC3G by Vpr was also detected in mammalian cells. Interestingly, however, the increased Vif protein level by Vpr did not result in more APOBEC3G degradation than without Vpr, indicating a potential regulatory effect of Vpr on Vif-mediated proteolysis of APOBEC3G.
CONCLUSIONTo our knowledge, this is the first report describing a potentially conserved and regulatory effect of HIV-1 Vpr on Vif and Vif-mediated protein degradation of APOBEC3G.
APOBEC-3G Deaminase ; Animals ; Cell Line ; Cytidine Deaminase ; biosynthesis ; metabolism ; Gene Expression ; Gene Products, vif ; biosynthesis ; metabolism ; Gene Products, vpr ; metabolism ; HIV-1 ; Humans ; Schizosaccharomyces ; genetics
4.Association between APOBEC3G polymorphisms and susceptibility to chronic hepatitis B.
Zhiyi YOU ; Fuyuan ZHOU ; Xionghu WANG ; Chuming CHEN ; Junhua ZHOU ; Dejian ZHAO ; Guifang HU
Journal of Southern Medical University 2013;33(5):769-771
OBJECTIVETo investigate the association between rs185983011 single-nucleotide polymorphisms (SNP) of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and the susceptibility to chronic hepatitis B.
METHODSThe blood samples were collected from 186 healthy subjects and 159 patients with chronic hepatitis B. The rs185983011 SNP was detected and genotyped by sequencing with Sanger's method to analyze the relationship between rs185983011 SNP and chronic hepatitis B.
RESULTSOnly C/C and C/T genotypes of the alleles of rs185983011 SNP were found in the tested subjects, and the C/C genotype was predominant (97.7%). The distribution frequencies of rs185983011 SNP genotypes and alleles showed no significant difference between healthy subjects and patients with chronic hepatitis B (P>0.05).
CONCLUSIONThe predominant genotype of rs185983011 SNP of APOBEC3G is C/C in the tested subjects, and rs185983011 SNP does not appear to associate with the susceptibility to chronic hepatitis B.
APOBEC-3G Deaminase ; Adult ; Alleles ; Case-Control Studies ; Cytidine Deaminase ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Hepatitis B, Chronic ; genetics ; Humans ; Male ; Polymorphism, Single Nucleotide ; Young Adult
5.Study on the relationship between human cytidine deaminase gene polymorphisms and Ara-C sensitivity.
Xiao-wen CHEN ; Li-jie YUE ; Cheng-rong LI ; Chang-gang LI ; Hong-song SHI ; Min ZHANG
Chinese Journal of Hematology 2008;29(7):459-463
OBJECTIVETo study the relationship between coding single-nucleotide polymorphisms (cSNPs) in the human cytidine deaminase (CDA) gene and cytosine arabinoside (Ara-C) sensitivity in childhood acute leukemia (AL).
METHODScDNAs from 87 leukemia and 199 control blood samples were analyzed for the cSNPs in CDA by PCR-denaturing gradient gel electrophoresis (DGGE) and sequencing. Human CDA genes were transformed into E. coli and yeast, respectively. Catalytic activities of the allele CDA and variant CDAs were determined by HPLC assay. The Ara-C sensitivity of the yeast transformants was measured by growth inhibition assays.
RESULTSThree known different polymorphisms, namely, 79A/C (K27Q), 208G/A (A70T) and 435T/C (silent) were identified in the coding region of CDA from an investigated Chinese population and displayed allelic frequencies of 12.1%, 0.5% and 76.2%, respectively. No association with susceptibility to disease was observed. Compared with that of CDA70A, the deamination activities for cytidine and Ara-C substrates of the E. coli transformants carrying human CDA70T were decreased by 53% and 63%, respectively (P<0.01), and the Ara-C IC50 value of the yeast transformants was also significantly decreased by 25% [(973 +/- 61) micromol/L to (735 +/- 31) micromol/L, P<0.05].
CONCLUSIONSThe 3 known cSNPs and their allelic frequencies of CDA are identified in a Chinese childhood AL. The 208A genotype is shown to be more sensitive to Ara-C than 208G genotype.
Cytarabine ; therapeutic use ; Cytidine Deaminase ; genetics ; Drug Resistance, Neoplasm ; Humans ; Leukemia ; drug therapy ; genetics ; Polymorphism, Single Nucleotide
6.Activation-induced Cytidine Deaminase in B Cell Immunity and Cancers.
Immune Network 2012;12(6):230-239
Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. These two genetic processes endow Abs with protective functions against a multitude of antigens (pathogens) during humoral immune responses. In B cells, AID expression is regulated at the level of either transcriptional activation on AID gene loci or post-transcriptional suppression of AID mRNA. Furthermore, AID stabilization and targeting are determined by post-translational modifications and interactions with other cellular/nuclear factors. On the other hand, aberrant expression of AID causes B cell leukemias and lymphomas, including Burkitt's lymphoma caused by c-myc/IgH translocation. AID is also ectopically expressed in T cells and non-immune cells, and triggers point mutations in relevant DNA loci, resulting in tumorigenesis. Here, I review the recent literatures on the function of AID, regulation of AID expression, stability and targeting in B cells, and AID-related tumor formation.
B-Lymphocytes
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Burkitt Lymphoma
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Cell Transformation, Neoplastic
;
Cytidine
;
Cytidine Deaminase
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DNA
;
Genetic Processes
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Germinal Center
;
Hand
;
Immunity, Humoral
;
Immunoglobulins
;
Leukemia, B-Cell
;
Lymphoma
;
Point Mutation
;
Protein Processing, Post-Translational
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Recombination, Genetic
;
RNA, Messenger
;
T-Lymphocytes
;
Transcriptional Activation
7.Activation-induced Cytidine Deaminase in B Cell Immunity and Cancers.
Immune Network 2012;12(6):230-239
Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. These two genetic processes endow Abs with protective functions against a multitude of antigens (pathogens) during humoral immune responses. In B cells, AID expression is regulated at the level of either transcriptional activation on AID gene loci or post-transcriptional suppression of AID mRNA. Furthermore, AID stabilization and targeting are determined by post-translational modifications and interactions with other cellular/nuclear factors. On the other hand, aberrant expression of AID causes B cell leukemias and lymphomas, including Burkitt's lymphoma caused by c-myc/IgH translocation. AID is also ectopically expressed in T cells and non-immune cells, and triggers point mutations in relevant DNA loci, resulting in tumorigenesis. Here, I review the recent literatures on the function of AID, regulation of AID expression, stability and targeting in B cells, and AID-related tumor formation.
B-Lymphocytes
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Burkitt Lymphoma
;
Cell Transformation, Neoplastic
;
Cytidine
;
Cytidine Deaminase
;
DNA
;
Genetic Processes
;
Germinal Center
;
Hand
;
Immunity, Humoral
;
Immunoglobulins
;
Leukemia, B-Cell
;
Lymphoma
;
Point Mutation
;
Protein Processing, Post-Translational
;
Recombination, Genetic
;
RNA, Messenger
;
T-Lymphocytes
;
Transcriptional Activation
8.Single-nucleotide polymorphisms of the cytidine deaminase gene in childhood with acute leukemia and normal Chinese children.
Li-jie YUE ; Xiao-wen CHEN ; Cheng-rong LI ; Chang-gang LI ; Hong-song SHI ; Min ZHANG
Chinese Journal of Medical Genetics 2007;24(6):699-702
OBJECTIVECytidine deaminase (CDA) is a key enzyme for metabolizing chemotherapeutic agent cytosine arabinoside (Ara-C), a deoxycytidine analog used for treatment of acute leukemia and lymphomas. Significant variability in the antitumor efficacy and systemic toxicity of Ara-C has been observed in cancer patients. Two missense mutations changing Ara-C sensitivity and toxicity had been found in the human CDA. Coding single-nucleotide polymorphisms (cSNPs) of CDA had been investigated in Japanese, Europeans Africans and Americans, but not in Chinese. The purpose of this study was to survey the allelic frequencies of CDA cSNPs in Chinese children.
METHODSThe bone marrow samples from 87 childhood patients with acute leukemia and peripheral blood samples from 199 non-malignancy-bearing children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for the polymorphisms in CDA by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE), PCR-restriction fragment length polymorphism (RFLP) and direct-sequencing. The distributive difference of each genotype was evaluated between children with acute leukemia and control children.
RESULTSThree known different polymorphisms, namely, 79A to C (K27Q), 208G to A (A70T) and 435T to C (silent) were identified in the coding region of CDA from the investigated Chinese population and displayed allelic frequencies of 12.1%, 0.52% and 76.2%, respectively. No association with susceptibility to disease was observed.
CONCLUSIONThis study demonstrates 3 cSNPs and their allelic frequencies of CDA in Chinese children, and provides the first step to identify genetic markers for predicting variability in Ara-C response and toxicity.
Acute Disease ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; Cytidine Deaminase ; genetics ; Female ; Humans ; Infant ; Infant, Newborn ; Leukemia ; genetics ; pathology ; Male ; Polymorphism, Single Nucleotide
9.Polymorphisms of IL-4, IL-4R alpha, and AICDA genes in adult allergic asthma.
Tianpen CUI ; Lin WANG ; Jianmin WU ; Lihua HU ; Jungang XIE
Journal of Huazhong University of Science and Technology (Medical Sciences) 2003;23(2):134-137
The relationship between 3 polymorphisms sites [interleulin-4 (IL-4), IL-4 receptor (IL-4R) alpha chain and activation-induced cytidine deaminase (AICDA)] and adult allergic asthma in China was studied. By using case-control method, DNA and clinical data were obtained from allergic asthmatic patients and compared with those in the control subjects. The subjects were genotyped for the IL-4 C-589T promoter polymorphism, the IL-4R alpha chain Q576R and the AICDA C8408T by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results showed that the IL-4 C-589T was not associated with adult allergic asthma in China. However, the IL-4R alpha chain 576R/R and AICDA 8408T/T frequency was significantly increased in allergic asthma group as compared with that in the control group [odd ratio (OR) = 3.797 and 9.127, respectively; P < 0.01)] and was correlated with the increased plasma total IgE. These data suggested that the IL-4R alpha chain 576R/R and AICDA 8408T/T genotypes confer genetic susceptibility to adult allergic asthma in China.
Adult
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Alleles
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Asthma
;
etiology
;
genetics
;
Cytidine Deaminase
;
genetics
;
Humans
;
Immunoglobulin E
;
blood
;
Interleukin-4
;
genetics
;
Phenotype
;
Polymorphism, Restriction Fragment Length
;
RNA Processing, Post-Transcriptional
;
Receptors, Interleukin-4
;
genetics
10.Polymorphisms of IL-4, IL-4R alpha, and AICDA genes in adult allergic asthma.
Tianpen, CUI ; Lin, WANG ; Jianmin, WU ; Lihua, HU ; Jungang, XIE
Journal of Huazhong University of Science and Technology (Medical Sciences) 2003;23(2):134-7
The relationship between 3 polymorphisms sites [interleulin-4 (IL-4), IL-4 receptor (IL-4R) alpha chain and activation-induced cytidine deaminase (AICDA)] and adult allergic asthma in China was studied. By using case-control method, DNA and clinical data were obtained from allergic asthmatic patients and compared with those in the control subjects. The subjects were genotyped for the IL-4 C-589T promoter polymorphism, the IL-4R alpha chain Q576R and the AICDA C8408T by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results showed that the IL-4 C-589T was not associated with adult allergic asthma in China. However, the IL-4R alpha chain 576R/R and AICDA 8408T/T frequency was significantly increased in allergic asthma group as compared with that in the control group [odd ratio (OR) = 3.797 and 9.127, respectively; P < 0.01)] and was correlated with the increased plasma total IgE. These data suggested that the IL-4R alpha chain 576R/R and AICDA 8408T/T genotypes confer genetic susceptibility to adult allergic asthma in China.
Alleles
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Asthma/etiology
;
Asthma/*genetics
;
Cytidine Deaminase/*genetics
;
Immunoglobulin E/blood
;
Interleukin-4/*genetics
;
Phenotype
;
*Polymorphism, Restriction Fragment Length
;
RNA Processing, Post-Transcriptional
;
Receptors, Interleukin-4/*genetics