Biology subjects

Arvidsson, G.

Publications and source records attributed to Arvidsson, G..

4 recordsLinked to original sources

bioRxiv2025

Interferon-α-Driven Stratification of B Cell Reveals Metabolic Reprogramming of Double Negative, Naive and Transitional cell subsets and Refines Molecular Classification in Söjgren's Disease.

Sjogrens disease (SjD) is a chronic autoimmune condition marked by lymphocytic infiltration of exocrine glands and production of autoantibodies such as anti-SSA/Ro, anti-SSB/La, and rheumatoid factor. B lymphocytes play a central role in disease pathogenesis, driving autoantibody production and glandular damage, and contributing to lymphomagenesis. Despite promising therapies, no effective treatment is currently available, partly due to the biological and clinical heterogeneity of the disease. While interferon (IFN) signatures and B cell-related markers are used for patient stratification, their integration remains unexplored. This study analyzed B cell transcriptional and metabolic profiles using bulk transcriptomic, clinical, and flow cytometry data from the PRECISESADS consortium, alongside public single-cell RNA-sequencing datasets. A B cell-specific IFN- signature was established to stratify patients into IFN-positive and IFN-negative groups. Both showed reduced oxidative phosphorylation (OXPHOS) and translation in B cell subsets, suggesting a shared pre-metabolic state. IFN-positive patients, however, displayed additional features, including enhanced glycolysis, amino acid and lipid metabolism, autophagy, and NF-{kappa}B signaling. They also showed an expansion of IFN-activated naive (Naive IFN), Transitional, and double-negative (DN) B cells, particularly DN2 and DN2_CXCR3 subsets, which have been linked in the literature to autoreactivity and lymphoma development. The IFN signature in naive B cells and DN2 correlated with elevated anti-SSA/Ro and anti-SSB/La titers, while only naive B cells showed an association with increased histological focus scores. These findings support the relevance of a B cell-specific IFN signature in stratifying SjD patients and suggest new metabolic and transcriptional targets for disease monitoring and therapeutic development. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/672530v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@fd8a4eorg.highwire.dtl.DTLVardef@183241dorg.highwire.dtl.DTLVardef@b7f2d9org.highwire.dtl.DTLVardef@a89349_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

A complete digital karyotype of the B-cell leukemia REH cell line resolved by long-read sequencing

The B-cell acute lymphoblastic leukemia (ALL) cell line REH, with the t(12;21) ETV6-RUNX1 translocation, is known to have a complex karyotype defined by a series of large-scale chromosomal rearrangements. Taken from a 15-year-old at relapse, the cell line offers a practical model for the study of high-risk pediatric B-ALL patients. In recent years, short-read DNA and RNA sequencing have emerged as a complement to analog karyotyping techniques in the resolution of structural variants in an oncological context. However, it is challenging to create a comprehensive digital karyotype of a genome with these techniques alone. Here, we explore the integration of long-read PacBio and Oxford Nanopore whole genome sequencing (WGS), IsoSeq RNA-sequencing, and short-read sequencing to create a detailed digital karyotype of the REH cell line. WGS refined the breakpoints of known aberrations and clarified the molecular traits of disrupted ALL-associated genes BTG1 and TBL1XR1, as well as the glucocorticoid receptor NR3C1. Several previously underreported structural variants were also uncovered, including deletions affecting the ALL-associated genes VPREB1 and NFATC1. Meanwhile, transcriptome sequencing identified seven fusion genes within the genomic breakpoints. Together, our extensive whole-genome investigation makes high-quality open-source data available to the leukemia genomics community. KEY POINTSO_LIA complete digital karyotype of the REH cell line was produced with short- and long-read DNA and RNA sequencing technologies. C_LIO_LIThe study enabled precise identification of structural variants, and the fusion genes expressed as the result of these variants. C_LI

cancer biology↗

bioRxiv2020

Differential transcriptional reprogramming by wild type and lymphoma-associated mutant MYC proteins as B-cells convert to lymphoma-like cells

The transcription factor MYC regulates the expression of a vast number of genes and is implicated in various human malignancies, for which its deregulation by genomic events such as translocation or amplification can be either disease-defining or associated with poor prognosis. In hematological malignancies MYC is frequently subject to missense mutations and one such hot spot where mutations have led to increased protein stability and elevated transformation activity exists within its transactivation domain. Here we present and characterize a model system for studying the effects of gradually increasing MYC levels as B-cells progress to lymphoma-like cells. Inclusion of two frequent lymphoma-associated MYC mutants (T58A and T58I) allowed for discrimination of changes in the MYC regulatory program according to mutation status. Progressive increase in MYC levels significantly altered the transcript levels of 7569 genes and subsets of these were regulated differently in mutant MYC proteins compared to WT MYC or between the mutant MYC proteins. Functional classification of the differentially regulated genes based on expression levels across different MYC levels confirmed previously found MYC regulated functions such as ribosome biogenesis and purine metabolism while other functional groups such as the downregulation of genes involved in B-cell differentiation and chemotaxis were novel. Gene sets that were differently regulated in cells overexpressing mutant MYC proteins contained an over-representation of genes involved in DNA Replication and transition from the G2 phase to mitosis. The cell model presented here mimics changes seen during lymphoma development in the E-Myc mouse model as well as MYC-dependent events associated with poor prognosis in a wide range of human cancer types and therefore constitutes a relevant cell model for in vitro mechanistic studies of wild type and mutant MYC proteins in relation to lymphoma development.

cancer biology↗

bioRxiv2020

Differential B-cell receptor signaling requirement for adhesion of mantle cell lymphoma cells to stromal cells

Interactions between lymphoma cells and stromal cells play a key role in promoting tumor survival and development of drug resistance. We identified differences in key signaling pathways between the JeKo-1 and REC-1 mantle cell lymphoma (MCL) cell lines, which exhibited different patterns of stromal cell adhesion and chemotactic migration towards stroma-conditioned medium. The identified adhesion-regulated genes reciprocated important aspects of microenvironment-mediated gene modulation in MCL patients. 590 genes were differently regulated between the cell lines upon adhesion to stromal cells, while 32 genes were similarly regulated in both cell lines. Regulation of B-cell Receptor (BCR) signature genes in adherent cells was specific for JeKo-1. Inhibition of BCR signaling by siRNA or clinically approved inhibitors, Ibrutinib and Acalabrutinib, decreased adhesion of JeKo-1 but not REC-1 cells to stromal cells. Cell surface levels of CXCR4 were higher in JeKo-1 cells and CXCR4 was important for migration and adhesion of JeKo-1 but not REC-1 cells. Surface levels of ICAM1 adhesion protein differ for REC-1 and JeKo-1. While ICAM1 plays a positive role in adherence of both cell lines to stromal cells, S1PR1 had an inhibitory effect. The results presented here provide a model framework for further investigation of mechanistic differences in patient-response to new pathway-specific drugs.

cancer biology↗