Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Systemic Lupus Erythematosus (SLE) is characterized by B cells lacking IgD and CD27 (double negative; DN). We show that DN cell expansions reflected a subset of CXCR5 CD11c cells (DN2) representing pre-plasma cells (PC). DN2 cells predominated in African-American patients with active disease and nephritis, anti-Smith and anti-RNA autoantibodies. They expressed a T-bet transcriptional network; increased Toll-like receptor-7 (TLR7); lacked the negative TLR regulator TRAF5; and were hyper-responsive to TLR7. DN2 cells shared with activated naive cells (aNAV), phenotypic and functional features, and similar transcriptomes. Their PC differentiation and autoantibody production was driven by TLR7 in an interleukin-21 (IL-21)-mediated fashion. An in vivo developmental link between aNAV, DN2 cells, and PC was demonstrated by clonal sharing. This study defines a distinct differentiation fate of autoreactive naive B cells into PC precursors with hyper-responsiveness to innate stimuli, as well as establishes prominence of extra-follicular B cell activation in SLE, and identifies therapeutic targets.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217820 | PMC |
| http://dx.doi.org/10.1016/j.immuni.2018.08.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Patients with lymphoma are at increased risk of severe infections, including SARS-CoV-2, due to immune suppression. Using multidimensional spectral flow cytometry and serology, we characterized in-depth immune responses in 50 SARS-CoV-2 vaccinated lymphoma patients across12 lymphoma subtypes, treated with anti-CD20 antibody (aCD20) ± chemotherapy (CT) or CT alone. Compared to healthy control, aCD20±CT-treated patients exhibited distinct immune alterations, including elevated late-stage effector memory (EM3) CD4+, and terminally differentiated (EMRA) CD8+ T cells, reduced circulating T follicular helper (cTfh) cells, and increased dysfunctional DN3 B cells.
View Article and Find Full Text PDFSubtype-specific atypical B cell profiles in myasthenia gravis reveal distinct immunopathological pathways.
Front Immunol
July 2025
Department of Pharmacology & Physiology, George Washington University, Washington, DC, United States.
Introduction: Atypical B cell (atBC) subsets display significant heterogeneity across autoimmune diseases, complicating efforts to define their role and therapeutic potential. We hypothesized that this heterogeneity reflects the responses to specific immunopathology, resulting in disease-specific profiles. The myasthenia gravis (MG) subtypes acetylcholine receptor (AChR)-positive MG and muscle-specific kinase (MuSK)-positive MG provide an ideal model to explore atBCs due to the distinct immune mechanisms driven by IgG1-3 and IgG4 autoantibodies, respectively in the disease.
View Article and Find Full Text PDFA multi-omics resource of B cell activation reveals genetic mechanisms for immune-mediated diseases.
medRxiv
June 2025
Division of Immunology, Boston Children's Hospital, Harvard Medical School.
Most genetic variants that confer risk of complex immune-mediated diseases (IMDs) affect gene regulation in specific cell types. Their target genes and focus cell types are often unknown, partially because some effects are hidden in untested cell states. B cells play central roles in IMDs, including autoimmune, allergic, infectious, and cancer-related diseases.
View Article and Find Full Text PDFCirculating immunoregulatory B cell and autoreactive antibody profiles predict lack of toxicity to anti-PD-1 checkpoint inhibitor treatment in advanced melanoma.
J Immunother Cancer
May 2025
St John's Institute of Dermatology, School of Basic and Medical Biosciences and KHP Centre for Translational Medicine, Guy's Hospital, King's College London, London, UK
Background: The majority of patients with melanoma develop immune-related adverse events (irAEs), and over half do not respond to anti-PD-1 (Programmed cell death protein 1) checkpoint inhibitor (CPI) immunotherapy. Accurate predictive biomarkers for both response to therapy and development of irAEs are currently lacking in clinical practice. Here, we conduct deep immunophenotyping of circulating regulatory and class-switched B cell and antibody immune states in patients with advanced stage III/IV melanoma prior to and longitudinally during CPI.
View Article and Find Full Text PDFElevated transferrin receptor 1 promoting B-cell autoimmunity in systemic lupus erythematosus.
Int Immunopharmacol
June 2025
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Depar
Background: Transferrin receptor 1 (TFR1), a major iron receptor for immune cells, could impair T cell metabolism and function in systemic lupus erythematosus (SLE), leading us to investigate the effects of TFR1 and possible mechanisms on lupus B cells.
Methods: B cells from lupus mouse models and systemic lupus erythematosus (SLE) patients were evaluated using flow cytometry (FCM) for levels of TFR1, intracellular iron deposition, reactive oxygen species (ROS), lipid peroxidation, and B-cell subsets. Transcript levels of TFR1 were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and upstream regulatory molecules were identified by in vitro gene silencing.