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Expression of transcriptional factors in age-associated B cells

ABSTRACT: To gain insights into the nature of human age-associated B cells (ABCs), we sorted peripheral B cells from a patient with new-onset SLE and performed droplet-based scRNA-seq. Seven distinct clusters were revealed by unsupervised clustering with a two-dimensional uniform manifold approximation and projection (UMAP). These clusters were assigned to known peripheral B cell subsets including transitional B cells, naïve B cells, activated naïve B cells, ABCs, memory B cells, plasmablasts, and plasma cells by comparing differentially expressed genes with established landmark genes. ABCs preferentially expressed genes encoding key surface markers CD19, CD86, FCRLA, FCRL3/5, FCGR2B, MS4A1 and ITGAX. We found 43 differentially expressed TFs: 27 upregulated and 16 downregulated.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242615 | GEO | 2023/12/31

REPOSITORIES: GEO

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Transcriptomic analysis of human B cell responses to vaccination

Project description:Analysis of the gene expression profiles of naïve B cells, resting memory B cells (MBCs), activated B cells (ABCs) and antibody-secreting cells (ASCs) isolated from peripheral blood one week following influenza vaccination. Upon antigen exposure B cells eventually bifurcate into two distinct lineages, plasmablasts and memory B cells. We previously reported that plasmablasts or antibody-secreting cells (ASCs) could be transiently detected in blood shortly after infection or vaccination of humans. Here, we define the phenotype and the transcriptional program of a novel human antigen-specific B cell subset, referred to as activated B cells (ABCs). ABCs do not spontaneously secrete antibodies and possess a unique transcriptional profile that distinguishes them from ASCs and resting memory B cells. Clonal lineages present among day 7 ABCs persisted in blood for up to three months post-influenza immunization indicating that ABCs may be destined to join the long-term memory B cell pool. ABCs and ASCs can be clearly distinguished in blood following influenza and Ebola virus infections. Interrogating ABCs will expand our understanding of the differentiation, maturation and longevity of human B cell responses.

2015-12-31 | GSE68245 | GEO

Transcriptomic analysis of human B cell responses to vaccination

Project description:Analysis of the gene expression profiles of naÃ¯ve B cells, resting memory B cells (MBCs), activated B cells (ABCs) and antibody-secreting cells (ASCs) isolated from peripheral blood one week following influenza vaccination. Upon antigen exposure B cells eventually bifurcate into two distinct lineages, plasmablasts and memory B cells. We previously reported that plasmablasts or antibody-secreting cells (ASCs) could be transiently detected in blood shortly after infection or vaccination of humans. Here, we define the phenotype and the transcriptional program of a novel human antigen-specific B cell subset, referred to as activated B cells (ABCs). ABCs do not spontaneously secrete antibodies and possess a unique transcriptional profile that distinguishes them from ASCs and resting memory B cells. Clonal lineages present among day 7 ABCs persisted in blood for up to three months post-influenza immunization indicating that ABCs may be destined to join the long-term memory B cell pool. ABCs and ASCs can be clearly distinguished in blood following influenza and Ebola virus infections. Interrogating ABCs will expand our understanding of the differentiation, maturation and longevity of human B cell responses. Total RNA was isolated from 10,000 cells of each population.

2015-12-31 | E-GEOD-68245 | biostudies-arrayexpress

CD11c+ autoimmune-associated B cells have an increased phagocytosis activity and T cell activation which is regulated by metabolic intervention in lupus mice

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2023-12-31 | GSE242611 | GEO

Age-Associated B Cells are Heterogenous and Dynamic in Autoimmunity

Project description:Age-Associated B Cells (ABCs) are a population of CD11c+ and/or CD11b+ B cells expanded in autoimmune lupus. To understand potential heterogeneity within ABCs and the relationship of ABCs to other splenic B cell subsets, we performed scRNA-seq with 5' V(D)J and CITE-seq cell surface features using the 10x Genomics Chromium platform on total splenic CD19+ B cells sorted from lupus-prone MRL/lpr. We found that ABC are a distinct transcriptional lineage that resolved into two related clusters. Analysis of BCR heavy chains identified clones present in both ABC and plasmablast compartments. Inferred lineage trees based on V gene somatic hypermutation suggested that self-renewing ABC feed into the plasmablast compartment repeatedly while continuing to themselves undergo mutation and expansion.

2023-01-01 | GSE202110 | GEO

RNA-seq data of ABC from Bm12-induced lupus model

Project description:Age-associated B cells (ABCs) accumulate in systemic autoimmunity, and contributes to pathogenesis. ABCs are characterized by high expression of CD11c and T-bet. As a transcription factor, T-bet cannot be labeled in live cells with antibodies, so we constructed a reporter mouse strain in which fluorescent protein tdTomato fused to T-bet. Then we sorted ABCs (CD11c+T-bet+CD21- B cell) and non-ABCs (CD11c-T- bet- B cell) from the Bm12-induced lupus model for RNA sequencing.

2023-02-16 | E-MTAB-12568 | biostudies-arrayexpress

Gene expression analysis of FO B and ABCs of young and aged mice.

Project description:We report the global gene expression in follicular (FO) B cells and age/autoimmunity-associated B cells (ABCs). We found that Fc-receptor like (Fcrl) 5 was highly expressed in ABCs isolated from 50-week-old mice, compared to FO B cells. This study provides a basis for understanding the relationship between autoimmune diseases and Fcrl5 expression in B cells.

2023-09-14 | GSE237540 | GEO

CD164 and FCRL3 are highly expressed on CD4+CD26- T cells in Sezary syndrome; inverse correlation between CD164 and CD26 expression

Project description:Sezary syndrome (SS) represents a leukemic variant of cutaneous T cell lymphoma (CTCL) with circulating malignant CD4 T cells trafficking to the skin. The cell surface molecules present on malignant cells are also expressed on normal CD4 T cells. Therefore, we attempted to find a specific marker for malignant cells that would distinguish them from normal cells. Comprehensive microarray analysis of gene expression in the malignant cells indicated significantly increased levels of mRNA for cell surface markers CD164, a sialomucin found on human CD34+ hematopoietic stem cells, as well as FCRL3, a molecule present on a subset of human natural T regulatory cells. Both markers were increased in CD4 T cells from the SS patients compared to those from Mycosis Fungoides patients and healthy volunteers. Subsequent studies utilizing QPCR and flow cytometry confirmed the increased expression of CD164 and FCRL3 mainly in CD4+CD26- T cells of SS patients. Our results suggest that CD164 can serve as a marker for diagnosis as well as disease monitoring of CTCL/SS, whereas the FCRL3 expression correlates with disease progression.

2019-11-21 | GSE39041 | GEO

Role of SWEF proteins in ABC differentiation

Project description:Age/autoimmune-associated B cells (ABCs) are a T-bet dependent B cell subset, which accumulates prematurely in autoimmune settings. The molecular pathways that regulate ABCs in autoimmunity are largely unknown. The SWEF proteins include SWAP-70 and DEF6, a newly identified SLE risk variant. SWEF-deficient mice (double knock-out=DKO) develop a lupus like syndrome, which is accompanied by a marked expansion of ABCs. The accumulation of ABCs in DKO mice provided us with a unique opportunity to gain new insights into the molecular features that characterize the ABCs that prematurely expand in autoimmune conditions. Splenic Follicular B cells (FoB, B220+CD19+CD23+CD11c-CD11b-) and ABCs (B220+CD19+CD11c+CD11b+) were FACS sorted from >20 weeks old WT or DKO female mice and RNA-seq was employed to compare the transcriptome of DKO ABCs to that of FoB cells derived from either WT or DKO mice. Here we show that loss of SWEF proteins leads to altered gene expression in B cells independently of their differentiation state. In addition, a subset of genes was uniquely regulated in ABCs from DKO mice as compared to FoB cells from either WT or DKO mice. Ananlysis of the ATAC-seq experiment show that the ABCs that expand aberrantly in the DKO autoimmune setting exhibit a unique chromatin landscape and ABC-specific accessible loci displayed enrichment in AP-1/BATF, IRF, and T-bet binding motifs. Together our findings suggest that absence of SWEF proteins affects several key processes in ABCs. In particular, we observed alterations in a number of pathways involved in the control of cellular proliferation and inflammation, a finding that may play a crucial role in the premature accumulation of ABCs in DKOs and could distinguish them from non-autoimmune ABCs.

2018-03-01 | GSE99480 | GEO

Expression data from young and aged murine B cell subsets

Project description:The origin and nature of recently discovered age-associated B cells (ABCs) is under investigation. We used a microarray to examine the transcriptional signatures of ABCs, follicular B cells from aged mice (AFO), and follicular B cells from young mice (YFO).

2016-05-20 | GSE81650 | GEO

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