A5013345893- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Celiac Disease Research and Management
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Acute Lymphoblastic Leukemia research
- Childhood Cancer Survivors' Quality of Life
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Chronic Myeloid Leukemia Treatments
- Advanced biosensing and bioanalysis techniques
- Lung Cancer Research Studies
- Diabetes and associated disorders
- Renal and related cancers
- Helicobacter pylori-related gastroenterology studies
- Chronic Lymphocytic Leukemia Research
- Neuroendocrine Tumor Research Advances
- Microscopic Colitis
Oslo University Hospital
2017-2024
University of Oslo
2016-2024
Wellcome Sanger Institute
2017-2019
University of California, San Francisco
2016-2017
657 Oslo
2016
University of San Francisco
2015
Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4+ regulatory (Treg) memory (Tmem) T in mouse skin colon, their respective draining lymph nodes (LNs) spleen. In these tissues, we identified Treg cell subpopulations distinct degrees NLT phenotype. Subpopulation pseudotime ordering gene kinetics were consistent recruitment yet the initial NLT-priming LNs final stages...
Abstract Analysis of antibody repertoires by high-throughput sequencing is major importance in understanding adaptive immune responses. Our knowledge variations the genomic loci encoding immunoglobulin genes incomplete, resulting conflicting VDJ gene assignments and biased genotype haplotype inference. Haplotypes can be inferred using IGHJ6 heterozygosity, observed one third people. Here, we propose a robust novel method for determining haplotypes adapting Bayesian framework. extends...
Inactivation of the tumor suppressor gene encoding transcriptional regulator Ikaros (IKZF1) is a hallmark BCR-ABL1+ precursor B cell acute lymphoblastic leukemia (pre-B ALL). However, mechanisms by which functions as in pre-B ALL remain poorly understood. Here, we analyzed mouse model together with new inducible expression wild-type IKZF1 mutant human ALL. We performed integrated genome-wide chromatin and analyses identified target genes ALL, revealing novel conserved pathways associated...
Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGPs) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated PC longevity 15 untreated and 26 treated patients addition to 13 non-CeD controls performed RNA sequencing clonal inference transcriptomic analysis 3,251 single PCs. observed antigen-dependent V-gene selection stereotypic antibodies....
Germline variations in immunoglobulin genes influence the repertoire of B cell receptors and antibodies, such polymorphisms may impact disease susceptibility. However, knowledge genomic variation loci is scarce. Here, we report 25 potential novel germline IGHV alleles as inferred from rearranged naïve cDNA repertoires 98 individuals. Thirteen were selected for validation, out which ten successfully confirmed by targeted amplification Sanger sequencing non-B DNA. Moreover, detected a high...
Clonally related B cells infiltrate the brain, meninges, and cerebrospinal fluid of MS patients, but mechanisms driving B-cell response shaping immunoglobulin repertoires remain unclear. Here, we used single-cell full-length RNA-seq BCR reconstruction to simultaneously assess phenotypes, isotypes, constant region polymorphisms, paired heavy- light-chain in intrathecal cells. We detected extensive clonal connections between memory cell antibody-secreting (ASC) compartments observed clonally...
Autoantibodies against the enzyme transglutaminase 2 (TG2) are characteristic of celiac disease (CeD), and TG2-specific immunoglobulin (Ig) A plasma cells abundant in gut biopsies patients. Here, we describe corresponding population autoreactive B blood. Circulating IgA present untreated patients on a gluten-containing diet but not controls. They clonally related to small intestinal cells, they express gut-homing molecules, indicating that cell precursors. Unlike other IgA-switched negative...
Summary Non-lymphoid tissues (NLTs) harbour a pool of adaptive immune cells, the development and phenotype which remains largely unexplored. Here, we used single-cell RNA-seq to characterise CD4 + regulatory (Treg) memory (Tmem) T cells in mouse skin colon, respective draining lymph nodes spleen. From this data, modelled continuous lymphoid-to-NLT trajectory for Treg, reconstructed mechanisms cell migration NLT adaption. This revealed shared transcriptional programme priming both...
Reconstruction of antigen receptor sequences from single-cell RNA-sequencing (scRNA-seq) data allows the linking usage to full transcriptomic identity individual B lymphocytes, without having perform additional targeted repertoire sequencing (Rep-seq). Here we report BraCeR (freely available at https://github.com/teichlab/bracer/ ), an extension TraCeR [1], for reconstruction paired full-length B-cell and inference clonality scRNA-seq ( Supplementary Note 1 ).
ABSTRACT Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGP) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated PC longevity 15 untreated and 26 treated patients addition to 13 non-CeD controls, performed RNA-sequencing clonal inference transcriptomic analysis 3251 single PCs. observed antigen-dependent V-gene selection stereotypic...
By offering high sequencing speed and ultra-high-throughput at a low price, Illumina next-generation platforms have been widely adopted in recent years. However, an experiment with multiplexed library could be risk of molecular recombination, known as "index switching", which causes proportion the reads to assigned incorrect sample. It is reported that new advance, exclusion amplification (ExAmp) conjunction patterned flow cell technology introduced on HiSeq 3000/HiSeq 4000/HiSeq X systems,...
Abstract Analysis of antibody repertoires by high-throughput sequencing is major importance in understanding adaptive immune responses. Our knowledge variations the genomic loci encoding genes incomplete, mostly due to technical difficulties aligning short reads these highly repetitive loci. The partial results conflicting V-D-J gene assignments between different algorithms, and biased genotype haplotype inference. Previous studies have shown that haplotypes can be inferred taking advantage...
ABSTRACT Autoantibodies against the enzyme transglutaminase 2 (TG2) are characteristic of celiac disease (CeD), and TG2-specific IgA plasma cells abundant in gut biopsies patients. We here describe corresponding population autoreactive B blood. Circulating were found untreated patients on a gluten-containing diet but not controls. They clonally related to small intestinal cells, they expressed gut-homing molecules, indicating that cell precursors. Unlike other IgA-switched negative for CD27,...
Abstract Clonally related B cells infiltrate the brain, meninges and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients, but mechanisms driving B-cell response shaping immunoglobulin repertoires remain unclear. Here, we used single-cell full-length RNA-seq receptor reconstruction to simultaneously assess phenotypes, isotypes, constant region polymorphisms, paired heavy- light-chain in intrathecal B-lineage cells. We detected extensive clonal connections between memory cell...
Abstract Single-cell adaptive immune receptor repertoire sequencing (scAIRR-seq) offers the possibility to access nucleotide sequences of paired chains from T-cell receptors (TCR) or B-cell (BCR). Here we describe two protocols and downstream bioinformatic approaches that facilitate integrated analysis (TR) alpha/beta (TRA/TRB) AIRR-seq, RNA (RNAseq), immunophenotyping, antigen-binding information. To illustrate methodologies with a use case, how identify, characterize, track...
ABSTRACT Germline variations in immunoglobulin genes influence the repertoire of B cell receptors and antibodies, such polymorphisms may impact disease susceptibility. However, knowledge genomic variation loci is scarce. Here, we report 25 novel germline IGHV alleles as inferred from rearranged naïve cDNA repertoires 98 individuals. Thirteen were selected for validation, out which ten successfully confirmed by targeted amplification Sanger sequencing non-B DNA. Moreover, detected a high...
Abstract Ikaros is a zinc finger transcription factor required for B-cell development and proper hematopoiesis, an important tumor suppressor in developing lymphocytes. To understand the mechanism of function potentially develop new improved targeted therapies, it to elucidate downstream target genes involved. With this aim, we combine mouse models pre-B ALL vitro culture human patient-derived cells. A model with deletion fourth DNA-binding resulted loss function, limited set deregulated...
Abstract Inactivation of the transcriptional factor Ikaros (IKZF1) correlates with poor prognosis in progenitor B-cell acute lymphoblastic leukemia (pre-B ALL), and is a hallmark BCR-ABL1+ subgroup pre-B ALL. critical regulator hematopoietic development required for development, however mechanisms by which functions as tumor suppressor ALL remain poorly understood. We analyzed recently developed mouse models containing targeted deletions DNA-binding zinc finger domains together new model...
The phenotypes of B lineage cells that produce oligoclonal IgG in multiple sclerosis have not been unequivocally determined. Here, we utilized single-cell RNA-seq data intrathecal combination with mass spectrometry intrathecally synthesized to identify its cellular source. We found the produced matched a larger fraction clonally expanded antibody-secreting compared singletons. was traced back two related clusters cells, one comprising highly proliferating and other consisting more...