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Targeting BMI-1 to deplete antibody-secreting cells in autoimmunity

ABSTRACT: Targeting BMI-1 to deplete antibody-secreting cells in autoimmunity

PROVIDER: PRJNA999632 | ENA |

REPOSITORIES: ENA

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Targeting BMI-1 to deplete antibody-secreting cells in autoimmunity

Project description:We measured genes expression differences in antibody secreting cells from LynKO mice in following treatment with a BMI-1 inhibitor (PTC-028) or a vehicle control. BMI-1 inhibition lead to a reduction in antibody secreting cells in LynKO mice and in humans donors. We performed RNA sequencing to understand the impact of BMI-1 inhibition on antibody secreting cells in LynKO mice.

2023-10-05 | GSE239515 | GEO

Targeting BMI-1 to deplete antibody-secreting cells in autoimmunity.

Project description:ObjectivesB cells drive the production of autoreactive antibody-secreting cells (ASCs) in autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Sjögren's syndrome, causing long-term organ damage. Current treatments for antibody-mediated autoimmune diseases target B cells or broadly suppress the immune system. However, pre-existing long-lived ASCs are often refractory to treatment, leaving a reservoir of autoreactive cells that continue to produce antibodies. Therefore, the development of novel treatment methods targeting ASCs is vital to improve patient outcomes. Our objective was to test whether targeting the epigenetic regulator BMI-1 could deplete ASCs in autoimmune conditions in vivo and in vitro.MethodsUse of a BMI-1 inhibitor in both mouse and human autoimmune settings was investigated. Lyn -/- mice, a model of SLE, were treated with the BMI-1 small molecule inhibitor PTC-028, before assessment of ASCs, serum antibody and immune complexes. To examine human ASC survival, a novel human fibroblast-based assay was established, and the impact of PTC-028 on ASCs derived from Sjögren's syndrome patients was evaluated.ResultsBMI-1 inhibition significantly decreased splenic and bone marrow ASCs in Lyn -/- mice. The decline in ASCs was linked to aberrant cell cycle gene expression and led to a significant decrease in serum IgG3, immune complexes and anti-DNA IgG. PTC-028 was also efficacious in reducing ex vivo plasma cell survival from both Sjögren's syndrome patients and age-matched healthy donors.ConclusionThese data provide evidence that inhibiting BMI-1 can deplete ASC in a variety of contexts and thus BMI-1 is a viable therapeutic target for antibody-mediated autoimmune diseases.

| S-EPMC10550498 | biostudies-literature

Protein expression of women with varying BMI [Custom Antibody Array]

Project description:Protein expression was analyzed by antibody array for differences between women of varying BMI.

2016-11-01 | GSE88783 | GEO

Protein expression of women with varying BMI [Custom Antibody Array]

Project description:Protein expression was analyzed by antibody array for differences between women of varying BMI.

2016-11-01 | GSE88782 | GEO

Protein expression of women with varying BMI [Custom Antibody Array]

Project description:Protein expression was analyzed by antibody array for differences between women of varying BMI.

2016-11-01 | GSE88781 | GEO

Autoantigen-Autoantibody expression of women with varying BMI [Custom Antibody Array]

Project description:Autoantigen-Autoantibody expression was analyzed by antibody array for differences between women of varying BMI.

2016-11-01 | GSE88784 | GEO

Characterization of gene expression in antibody secreting cells

Project description:The CD19 positive antibody secreting cells (ASC) in both bone marrow (BM) have the capacity to provide immune memory in addition to cells traditionally considered long-lived, the CD19-negative BM ASC. We performed flow cytometry (FCM) immunophenotyping, fluorescence-activated cell sorting (FACS) for cell subset isolation, ELISpot assays detecting the isotype of antibody secretion as well as antibodies against vaccine derived antigens, and comparative gene expression analyses of CD19- ASC, CD19+ ASC, CD20- B cells, and CD20+ B cells from BM. The findings may aid in the understanding of the differential cell subsets created through vaccination and lead to improved vaccine strategies and production. FACS sorted tissue B cells and antibody secreting cell subset gene expression.

2018-12-03 | GSE107683 | GEO

Characterization of gene expression in antibody secreting cells

Project description:Characterization of gene expression in antibody secreting cells

| PRJNA421015 | ENA

Whole Transcriptome RNASeq Data for Cell-Sorted Antibody Secreting Cells (ASC)

Project description:We report whole transcriptome RNASeq data for cell-sorted pop2, pop3, and pop5 which are antibody-secreting cells from human peripheral blood

2018-07-12 | GSE116971 | GEO

Transcriptomic diversity and overlapping clonality across subsets of antibody-secreting and memory B cells from spontaneous germinal centers

Project description:Affinity matured self-reactive antibodies are found in autoimmune diseases like systemic lupus erythematous. Here we used fate-mapping reporter mice and single cell transcriptomics coupled to antibody repertoire analysis to characterize the post-germinal center (GC) B cell compartment in a new mouse model of autoimmunity. Antibody secreting cells (ASCs) and memory B cells (MemBs) from spontaneous GCs grouped into multiple subclusters. ASCs matured into two terminal clusters, with distinct secretion, antibody repertoire and metabolic profiles. MemBs contained FCRL5+ and CD23+ subsets, with different in vivo localization in the spleen. GC-derived FCRL5+ MemBs share transcriptomic and repertoire properties with atypical B cells found in aging and infection and localize to the marginal zone, suggesting a similar contribution to rapid recall responses. While transcriptomically diverse, ASC and MemB subsets maintained an underlying clonal redundancy. Therefore, self-reactive clones could escape subset-targeting therapy by perpetuation of self-reactivity in distinct subsets.

2023-06-22 | GSE203132 | GEO

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