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To map a potential locus corresponding to the CD23low phenotype

ABSTRACT: CD23, the low affinity receptor for IgE, has been proposed to play a critical role in the regulation of IgE production, based on altered IgE levels in CD23-deficient mice and transgenic mouse models, as well as in mouse strains with mutations in the CD23 gene, e.g. 129 substrains. Here, we have investigated a mouse line termed LxT1 that expresses reduced CD23 surface levels on B cells, and its influence on IgE production. Extensive phenotypic analyses showed that CD23 surface expression was reduced in LxT1 compared to the control, without affecting B cell development in general. We linked the CD23low surface level in LxT1 mice to a recessive locus, a 129-derived region spanning 28Mb on chromosome 8, which includes the CD23 gene. Sequence analysis confirmed the five mutations within the CD23 coding region in LxT1 mice, the same as those present in NZB and 129 substrains. However, this CD23low phenotype was not observed in all 129 substrains despite carrying these same CD23 mutations in the coding region. Affymetrix Mouse Diversity Genotyping Array was performed according to the manufacturer's directions on DNA extracted from crossed mice samples. The array can interrogate more than 623,000SNPs, yielding an average SNP density of one marker per 4.3kb. Genetic linkage analysis was performed to exploit the co-segregation of chromosomal regions with the CD23 phenotype to identify the location of causative genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE44231 | GEO | 2013/02/12

SECONDARY ACCESSION(S): PRJNA189220

REPOSITORIES: GEO

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To map a potential locus corresponding to the CD23low phenotype

Project description:CD23, the low affinity receptor for IgE, has been proposed to play a critical role in the regulation of IgE production, based on altered IgE levels in CD23-deficient mice and transgenic mouse models, as well as in mouse strains with mutations in the CD23 gene, e.g. 129 substrains. Here, we have investigated a mouse line termed LxT1 that expresses reduced CD23 surface levels on B cells, and its influence on IgE production. Extensive phenotypic analyses showed that CD23 surface expression was reduced in LxT1 compared to the control, without affecting B cell development in general. We linked the CD23low surface level in LxT1 mice to a recessive locus, a 129-derived region spanning 28Mb on chromosome 8, which includes the CD23 gene. Sequence analysis confirmed the five mutations within the CD23 coding region in LxT1 mice, the same as those present in NZB and 129 substrains. However, this CD23low phenotype was not observed in all 129 substrains despite carrying these same CD23 mutations in the coding region. Affymetrix Mouse Diversity Genotyping Array was performed according to the manufacturer's directions on DNA extracted from crossed mice samples. The array can interrogate more than 623,000SNPs, yielding an average SNP density of one marker per 4.3kb. Genetic linkage analysis was performed to exploit the co-segregation of chromosomal regions with the CD23 phenotype to identify the location of causative genes. To map a potential mutation, male LxT1 mice were crossed to female BALB/c mice to generate F1 mice. Two females from the F1 litters were backcrossed to the parental male LxT1 to generate N2 mice for analysis of phenotype and genetic mapping. N2 mice with (n=6) and without (n=5) CD23low surface level and (n=1) BALB/c were used to map putative genetic alteration that may cause the CD23low phenotype.

2013-02-12 | E-GEOD-44231 | biostudies-arrayexpress

CD23+IgG1+ memory B cells are poised to switch to pathogenic IgE production in food allergy

Project description:Food allergy is caused by allergen-specific IgE but little is known about the B cell memory of persistent responses. Here we describe in pediatric peanut allergy a population of CD23+IgG1 memory B cells that contains peanut-specific clones and generates IgE plasma cells on activation. Through single cell transcriptomics and B cell receptor (BCR) sequencing, we characterized FCER2/CD23+ IgG1 memory B cells co-expressing IL4R, IL13RA1, IGHE and carrying highly mutated BCRs. Further we found that peanut allergen (Ara h 2)-specific B cells were mostly IgG1 memory cells, carried highly mutated BCRs compared to diphtheria toxin-specific B cells, and expressed FCER2 and germlin IGHE. Our findings suggest that CD23+IgG1+ memory B cells transcribing IGHE are a unique memory population containing precursors for pathogenic IgE in food allergy.

2023-11-16 | GSE208235 | GEO

T Cell Intrinsic Responses to TGFβ Regulates Allergen Sensitization By Modulating Type 2 T Follicular Helper Cell Development

Project description:Immunoglobulin E (IgE) is a potent mediator of allergic diseases, but the mechanisms that regulate IgE responses to innocuous environmental and food antigens remain unclear. Patients with Loeys-Dietz syndrome (LDS) who have mutations in genes encoding the TGFβ receptor are predisposed to IgE-mediated disorders. Here, using patient samples and a mouse model, we demonstrate that LDS mutations lead to reduced canonical TGFβ signaling, elevated total and allergen-specific IgE, increased type 2 follicular helper T cells (Tfh2), and exaggerated germinal center activity that was not prevented by the presence of wild type T regulatory cells. T cell intrinsic defects in LDS mice resulted in spontaneous sensitization to orally administered OVA, and inhibition of mammalian target of rapamycin (mTOR) prevented the exaggerated Tfh and IgE responses to OVA. Thus, TGFβ limits human and mouse Tfh2 cell development via the phosphatidylinositol-3-OH kinase gamma (PI3Kg)/AKT/mTOR pathway, and disruption of this pathway promotes allergic inflammation.

2023-08-01 | GSE202688 | GEO

T Cell Intrinsic Responses to TGFβ Regulates Allergen Sensitization By Modulating Type 2 T Follicular Helper Cell Development

2023-08-01 | GSE203379 | GEO

Identification of common lupus-disease related microRNA expression pattern in three different murine models of lupus

2011-12-17 | GSE22359 | GEO

Identification of common lupus-disease related microRNA expression pattern in three different murine models of lupus

Project description:In this study, miRNA expression in splenic lymphocytes from three genetically disparate lupus-prone mouse models (MRL-lpr, B6-lpr and NZB/WF1) were profiled. 49 miRNAs were found to be differentially expressed in MRL-lpr mice compared to MRL mice; and 24 miRNAs were differentially expressed in B6-lpr mice compared to B6 mice. Among these dysregulated miRNAs, we noted that 15 miRNAs were common to both lpr strains. Interestingly, microarray analysis of NZB/W and NZW at 3 months of age, an age when overt lupus disease is not evident in NZB/W mice, revealed that only one miRNA, miR-148a was significantly upregulated in NZB/W mice. The aim of this porject is to determine the common miRNA expression changes in splenocytes from different strains of murine lupus models. The splenocytes were prepared from genetically lupus-prone female mice including MRL/MpJ-Faslpr/J (MRL-lpr), NZBWF1/J (NZB/W), B6.MRL-Faslpr/J (B6-lpr) and their control mice MRL/MpJ (MRL), NZW/LacJ (NZW) and C57BL/6J (B6) mice (The Jackson laboratory, ME). Total RNAs, containing miRNAs were isolated from whole splenocytes using mirVana miRNA isolation kits (Ambion) following manufactory’s instructions and sent to LC Sciences (http://www.lcsciences.com/) for the microarray assay. The mouse miRNA array chips (Chip ID miRMouse 12.0 version), which included 617 unique, mature, mouse miRNA, based on the Sanger miRBase Release 12.0, were used in the assay.

2011-12-17 | E-GEOD-22359 | biostudies-arrayexpress

RNAseq analysis of two independent stains of C57BL/6J-Plat-/- mice and wild-type C57BL/6J.

Project description:The ability to generate defined null mutations in mice revolutionized the analysis of gene function in mammals. However, gene-deficient mice generated by using 129-derived embryonic stem (ES) cells may carry large segments of 129 DNA, even when extensively backcrossed to reference strains, such as C57BL/6J, and this may confound interpretation of experiments performed in these mice. Tissue plasminogen activator (tPA), encoded by the PLAT gene, is a fibrinolytic serine protease that is widely expressed in the brain. A large number of neurological abnormalities have been reported in tPA-deficient mice. The studies here compare genes differentially expressed in the brains of Plat-/- mice from two independent Plat-/- mouse derivations to wild-type C57BL/6J mice. One strain denoted “Old” was constructed in ES cells from a 129 mouse and backcrossed extensively to C57BL/6J, and one denoted “New” Plat-/- mouse was constructed using zinc finger nucleases directly in the C57BL/6J-Plat-/- mouse strain. We identify a significant set of genes that are differentially expressed in the brains of Old Plat-/- mice that preferentially cluster in the vicinity of Plat on chromosome 8, apparently linked to more than 20 Mbp of DNA flanking Plat being of 129 origin. No such clustering is seen in the New Plat-/- mice.

2016-12-16 | GSE76093 | GEO

Effect of Sirolimus treatment on lupus nephritis in NZB/W F1 female mice

Project description:NZB/WF1 female mice spontaneously develop autoimmune lupus nephritis. Expression profiling of kidney tissue from (a) 12 week NZB/W F1 female mice defined as asymptomatic for lupus nephritis, (b) 36 and 42 week NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 and 42 week NZB/W F1 female mice that are diseased/symptomatic for lupus nephritis and treated with Sirolimus was carried out. The goal of the study was to identify genes associated with lupus nephritis and modulated by Sirolimus, an inhibitor of mTOR. In addition, lupus nephritis genes resistant to Sirolimus therapy were also identfied This series of samples comprises of kidney tissue from (a) 12 week old NZB/W F1 female mice defined as asymptomatic for lupus nephritis (N=4), (b) 36 (N=3) and 42 week (N=3) old NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 (N=3)and 42 (N=3) week old NZB/W F1 female mice that are asymptomatic for lupus nephritis on treatment with Sirolimus

2008-11-20 | E-GEOD-12024 | biostudies-arrayexpress

Protein profiling of human serum against a panel of allergens.

Project description:Current diagnostics for allergies, such as skin prick and radioallergosorbent tests, do not allow for inexpensive, high-throughput screening of patients. Additionally, extracts used in these methods are made from washed pollen that lacks pollen surface materials that may contain allergens. We sought to develop a high-throughput assay to rapidly measure allergen-specific IgE levels in sera and to explore the relative allergenicity of different pollen fractions (i.e. surface, cytoplasmic, commercial extracts). To do this, we generated a protein microarray containing surface, cytoplasmic, and commercial extracts from 22 pollen species, commercial extracts from nine non-pollen allergens, and five recombinant allergenic proteins. Arrays were incubated with <25uL of serum from 176 individuals and bound IgE was detected by indirect immunofluorescence, providing a high-throughput measurement of IgE levels.

2010-09-08 | E-MTAB-177 | biostudies-arrayexpress

Type 2-polarized memory B cells hold allergen-specific IgE memory

Project description:Allergen-specific IgE antibodies mediate allergic pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. We report a population of type 2 polarized MBCs defined as CD23hi, IL-4Rαhi, CD32low at the transcriptional and surface protein levels.

2023-11-25 | GSE248256 | GEO

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