Single cell Ig VDJ sequencing (10X Genomics) of human blood B cells from SLE pateints and healthy controls
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE183051 | GEO | 2022/01/26
REPOSITORIES: GEO
Similar Datasets
Project description:<p>Follicular lymphoma (FL) is a generally incurable B-cell malignancy which has the potential to transform into highly aggressive lymphomas. Genomic studies indicate it is often a small subpopulation rather than the dominant population in the FL that gives rise to the more aggressive subtype. To resolve the underlying transcriptional networks of follicular B-cell lymphomas at single molecule and cell resolution, we leveraged droplet-based barcoding technology for highly parallel single cell RNA-Seq. We analyzed the transcriptomes from tens of thousands of cells derived from five primary FL tumors. Simultaneously, we conducted multi-dimensional flow cell sorting to validate our characterizing of cellular lineages and critical expressed proteins. For each tumor, we identified multiple cellular subpopulations, matching known hematopoietic lineages. Comparison of gene expression by matched malignant and normal B cells from the same patient revealed tumor-specific features. Malignant B cells exhibited restricted immunoglobulin light chain expression (either Ig Kappa or Ig Lambda), as well the expected upregulation of the BCL2 gene, but also down-regulation of the FCER2, CD52 and MHC class II genes. By leveraging the single-cell resolution on large numbers of cells per patient, we were able to examine tumor-resident T cells. We identified pairs of immune checkpoint molecules that were co-expressed, providing a potentially useful strategy for selection of patient-tailored combination immunotherapies. In summary, massively parallel measurement of single-cell expression in thousands of tumor cells and tumor-resident lymphocytes can be used to obtain a systems-level view of the tumor microenvironment and identify new avenues for therapeutic development.</p>
| phs001378 | dbGaP
Project description:The activation signaling of transcription factor nuclear factor-kB (NF-kB) plays central role for immune system. One of key kinase mediating this pathway is TAK1 in adaptive and innate immunity. However, role of TAK1 in bone marrow B cell is still unclear. To know effects of TAK1-deletion, the gene expression of Ig-lambda/kappa positive cells were analyzed in comparison of wild type with TAK1-deficient bone marrow B cells.
2015-10-22 | GSE74248 | GEO
Project description:Cells from four develppmental stages were purified by FACS from human bone marrow samples Experiment Overall Design: Cells were sorted as follows: PB1: CD34+VpreB+ PB2: VpreB-CD34+ LAR: kappa/lambda-VpreB-large SMA: kappa/lambda-VpreB-small. All cells were CD19+
2008-06-18 | E-GEOD-4590 | biostudies-arrayexpress
Project description:Single cell Ig VDJ sequencing (10X Genomics) of human blood B cells from SLE pateints and healthy controls
| PRJNA758962 | ENA
Project description:Flow cytometry sorted B-cells reactive to ACE2 peptides isolated from peripheral blood of COVID-19 patients compared with non-reactive B-cells using pooled hashtag barcoding and 10x genomics 5'DGE kit and VDJ recombination of B-cells
2023-06-01 | GSE178123 | GEO
Project description:9G4+ IgG antibodies expand in SLE in a disease specific fashion and react with different lupus antigens including B cell antigens and apoptotic cells. Their shared use of VH4-34 represents a unique system to understand the molecular basis of lupus autoreactivity. Understanding the participation of apoptotic cells, a rich source of self-antigens including chromatin, in the diversification and selection of autoreactive memory B cells is particularly important in SLE where these cells accumulate in the germinal centers and may activate pathogenic autoreactive B cells. Our findings indicate that the three mabs with strong apoptotic binding recognized chromatin and individual histones as documented by glomerular proteome microarrays. While the actual antigens mediating APCB remain to be formally elucidating, our initial studies indicate that binding to histone/chromatin may mediate such autoreactivity in at least a fraction of these antibodies Single VH4-34 B cells sorted from IgD-CD27+ memory B cells of SLE patient are sorted and single -RT-PCR is performed to generate monoclonal antibody. 3 monoclonals which were strong apoptotic binders tested for protein array against Chromatin, Histone1, Histone 2A, Histone 2B, Histone 3, Histone 4 and total histones
2013-09-05 | E-GEOD-50609 | biostudies-arrayexpress
Project description:Objective: Gene expression studies performed on PBMC from systemic lupus erythematosus (SLE) patients provided strong evidence of a type I interferon signature, underscoring the potential role of these cytokines in the physiopathology of SLE. In this work, we performed microarray analyses of differential gene expression using purified CD4 T and B cells sorted from SLE PBMC. In order to discriminate genes specific to SLE from those induced by inflammatory responses in general, control samples were obtained not only from healthy individuals but also from rheumatoid arthritis (RA) patients. Results: A strong interferon signature was found both in the CD4 T and the B lymphocytes from SLE patients, thereby confirming the results obtained on total PBMC. Interestingly, many interferon-induced genes were also over-expressed in CD4 and B cells from RA patients. Some genes were more specifically over-expressed in SLE lymphocytes, and 3 of them, SLAMF1, BRDG1 and RASGRP1, were exclusively up-regulated in SLE B cells. SLAMF1 and BRDG1 are localized in disease-associated loci, thereby suggesting that they might play a role in the physiopathology of the disease. Experiment Overall Design: CD4 T and B cells were sorted by flow cytometry from PBMC of patients with SLE, RA and healthy controls. GeneChip® Human genome U133 Plus 2.0 arrays were hybridized in monoplicates and the genes differentially expressed among the three groups of patients were identified using ANOVA tests with corrections for multiple comparisons.
2008-06-13 | E-GEOD-4588 | biostudies-arrayexpress
Project description:Type I interferon (IFN), namely IFN- α, and B cell aberrations are long recognized in systemic lupus erythematosus (SLE) pathogenesis. Type I IFN receptor blockade has undergone clinical trials in SLE with varying degrees of success. Type III IFN (IFN-λ) produce a gene signature currently indistinguishable from that of type I in responsive cell types. IFN-λ are not blocked by type I IFN receptor blockade as they utilize a unique receptor (IFNLR1). Type III IFN are appreciated to have an important role in viral infection at epithelial barriers where IFNLR1 is strongly expressed. The effects of IFN-λ on immune cells remain understudied and are different between human and murine models. We have previously shown that human B cells can transcribe type I IFN genes after IFN-λ treatment including those associated with SLE. We have found that IFN-λ is detected in the serum of human SLE patients and correlates with IgD- CD27- CD21- CD24- (DN2) B cells, a compartment which contains CD11c+ age/autoimmunity B cells (ABC). ABC are a target of interest as recent studies suggest they are poised for plasma cell differentiation and enriched in autoreactivity and thus have the potential to contribute to SLE pathogenesis. Results: Naïve and DN cells display a prominent type I IFN gene expression profile in SLE. Transcript for type I, type II, and type III IFN receptors (IFNAR1, IFNAR2, IFNGR1, IFNGR2, IFNLR1, and IL10RB) are detected in HD and SLE B cells. CD11c+ CD21- frequency increased in DN compared to naïve B cells for SLE and HD (both p< 0.001). The mean and range of CD11c+ CD21- frequency was higher in SLE DN (30.7± 9.5%, mean±SEM; range 4.8-74.7%) compared to HD DN (7.6%±1.0%,3.6-9.4%). Increased IFNLR1 transcript correlated with CD11c+ CD21- B cell expansion (r2=0.922, p<0.0001). Increased pSTAT1 after IFN-α2 treatment is found in monocytes, T cells, and B cells but only in the B cells after IFN-λ1 treatment. Naïve, DN, switched, and unswitched memory HD B cells are responsive to type I and type III IFN, but demonstrated a higher pSTAT1 fold change with type I IFN treatment compared to type III IFN. In all B cell subsets, CD11c+ cells had a higher pSTAT1 fold change after IFN-λ1 stimulation than did CD11c- B cells. In HD with well-defined populations of CD11c+ CD21- DN cells, pSTAT1 fold change for IFN-λ approached that of IFN-α2. Conclusions: All human B cell subsets defined by CD27 and IgD respond to IFN-α and IFN-λ, but those expressing CD11c+ have increased responsiveness to IFN-λ. CD11c+ cells expand in SLE and associate with autoreactive plasma cell development. Thus, the role of IFN-λ may take on increased clinical significance in the setting type I IFN receptor blockade. These results suggest IFN-λ is an underappreciated driver of the IFN signature and B cell aberrations in SLE.
2021-08-28 | GSE175913 | GEO
Project description:We designed two different BCL2 deregulation models in transgenic mice, whereby the oncogene was either associated with the IgH3′RR superenhancer, as in t(14;18), or inserted into the kappa light chain locus. We compared the impact of these models on B-cell fate and lymphoid tissues. Linkage to the IgH superenhancer showed a quite specific impact on germinal center B cell populations. The Ig kappa model was much less specific and strongly boosted the plasma cell in-flow and the accumulation of long-lived plasma cells.
2022-11-10 | GSE217605 | GEO
Project description:We designed two different BCL2 deregulation models in transgenic mice, whereby the oncogene was either associated with the IgH3′RR superenhancer, as in t(14;18), or inserted into the kappa light chain locus. We compared the impact of these models on B-cell fate and lymphoid tissues. Linkage to the IgH superenhancer showed a quite specific impact on germinal center B cell popu-lations. The Ig kappa model was much less specific and strongly boosted the plasma cell in-flow and the accumulation of long-lived plasma cells.
2022-11-07 | GSE217095 | GEO