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Neu-medullocytes, sialidase-positive B cells in the thymus, express autoimmune regulator (AIRE).

ABSTRACT: Neu-medullocytes, which were previously identified and named by our group, are sialidase (neuraminidase)-positive B cells that express immunoglobulin and Mac-1 in the mouse thymus. Recently, B cells that migrated into the thymus were reported to express autoimmune regulator (AIRE) and to contribute to self-tolerance. We sought to determine whether Neu-medullocytes also express AIRE. We obtained positive results by triple staining Neu-medullocytes for in situ sialidase activity, anti-AIRE, and either anti-IgG or anti-IgM antibodies and observing the staining with confocal microscopy. Additional molecules including CD5, IgM, major histocompatibility complex (MHC) Class II, and neuraminidase 1 (NEU1) were found in sialidase-positive cells independently. The real-time PCR results suggest that the primary sialidase in AIRE-positive cells is neuraminidase 2 (NEU2). Furthermore, some of the AIRE-positive medullary thymic epithelial cells also clearly showed sialidase activity when a triple staining of sialidase activity, anti-AIRE, and Ulex europaeus agglutinin-1 (UEA-1) was performed. Neu-medullocytes may present Aire-dependent antigens for negative selection. We discuss the negative selection steps in consideration of sialidases and sialic acids.

SUBMITTER: Kijimoto-Ochiai S

PROVIDER: S-EPMC6351566 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Neu-medullocytes, sialidase-positive B cells in the thymus, express autoimmune regulator (AIRE).

Kijimoto-Ochiai Shigeko S Kamimura Keiko K Koda Toshiaki T

Scientific reports 20190129 1

Neu-medullocytes, which were previously identified and named by our group, are sialidase (neuraminidase)-positive B cells that express immunoglobulin and Mac-1 in the mouse thymus. Recently, B cells that migrated into the thymus were reported to express autoimmune regulator (AIRE) and to contribute to self-tolerance. We sought to determine whether Neu-medullocytes also express AIRE. We obtained positive results by triple staining Neu-medullocytes for in situ sialidase activity, anti-AIRE, and ei ...[more]

PMID: 30696872

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Project description:BackgroundThe autoimmune regulator (AIRE) is expressed in the thymus, particularly in thymic medullary epithelial cells (mTECs), and is required for the ectopic expression of a diverse range of peripheral tissue antigens by mTECs, facilitating their ability to perform negative selection of auto-reactive immature T-cells. The expression profile of peripheral tissue antigens is affected not only by AIRE deficiency but also with variation of AIRE activity in the thymus.Method and resultsTherefore we screened 591bp upstream of the AIRE transcription start site including AIRE minimal promoter for single nucleotide polymorphism (SNPs) and identified two SNPs -655R (rs117557896) and -230Y (rs751032) respectively. To study the effect of these variations on AIRE promoter activity we generated a Flp-In host cell line which was stably transfected with a single copy of the reporter vector. Relative promoter activity was estimated by comparing the luciferase specific activity for lysates of the different reporter AIRE promoter-reporter gene constructs including AIRE-655G AIRE-230C, AIRE-655G AIRE-230T and AIRE-655A AIRE-230C. The analysis showed that the commonest haplotype AIRE-655G AIRE-230C has the highest luciferase specific activity (p<0.001). Whereas AIRE-655G AIRE-230T has a luciferase specific activity value that approaches null. Both AIRE promoter polymorphic sites have one allele that forms a CpG methylation site which we determined can be methylated in methylation assays using the M.SssI CpG methyltransferase.ConclusionAIRE-230Y is in a conserved region of the promoter and is adjacent to a predicted WT1 transcription factor binding site, suggesting that AIRE-230Y affects AIRE expression by influencing the binding of biochemical factors to this region. Our findings show that AIRE-655GAIRE-230T haplotype could dramatically alter AIRE transcription and so have an effect on the process of negative selection and affect susceptibility to autoimmune conditions.

Dataset Information

Neu-medullocytes, sialidase-positive B cells in the thymus, express autoimmune regulator (AIRE).

Publications

Neu-medullocytes, sialidase-positive B cells in the thymus, express autoimmune regulator (AIRE).

Similar Datasets

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