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.
Pubmed ID: 30314758 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsSoftware package as a DESeq2- and EdgeR-Based R Pipeline for Comprehensive Differential Analysis of RNA-Seq Data.
View all literature mentionsThis polyclonal targets IgG-Fc Fragment
View all literature mentionsThis monoclonal targets Human CXCR5 Allophycocyanin MAb (Clone 51505)
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis polyclonal targets IgG-Fc Fragment
View all literature mentionsThis unknown targets Human IgG, whole molecule
View all literature mentionsThis unknown targets Human IgG
View all literature mentionsThis unknown targets Human IgG, F'2 Fragment Specific
View all literature mentionsThis monoclonal targets Human IgG3
View all literature mentionsThis monoclonal targets T-bet
View all literature mentionsThis monoclonal targets Stat3, phospho (Tyr705)
View all literature mentionsThis monoclonal targets Stat1, phospho (Tyr701)
View all literature mentionsThis monoclonal targets CD319
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis monoclonal targets IRF8
View all literature mentionsThis monoclonal targets IRF4
View all literature mentionsThis monoclonal targets IgD
View all literature mentionsThis monoclonal targets CD307e
View all literature mentionsThis monoclonal targets CD307d
View all literature mentionsThis monoclonal targets ERK1/2 (pT202/pY204)
View all literature mentionsThis monoclonal targets CD86 (B7-2)
View all literature mentionsThis monoclonal targets CD72
View all literature mentionsThis monoclonal targets Human CD62L
View all literature mentionsThis monoclonal targets CD38
View all literature mentionsThis monoclonal targets CD3e
View all literature mentionsThis monoclonal targets CD27
View all literature mentionsThis monoclonal targets CD24
View all literature mentionsThis monoclonal targets CD21
View all literature mentionsThis monoclonal targets CD20 (cytoplasmic)
View all literature mentionsThis monoclonal targets CD19
View all literature mentionsThis monoclonal targets CD14
View all literature mentionsThis monoclonal targets CD138
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis unknown targets BLNK, phospho (Tyr84)
View all literature mentionsA cloud-based platform which allows users to analyze, visualize, and archive multiparamter cytometry data for single-cell biology. Multiple single-cell data sets can be analyzed and visualized simultaneously with a variety of graphics, inlcuding Sunburst, SPADE, and viSNE. Users can store and back up related data such as protocols, microscopy images, and presentations and collaborate and share analysis and data sets with other Cytobank users. Cytobank also provides a variety of services and training sessions to assist with experiment workflow.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsSoftware tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.
View all literature mentionsOriginal SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsCell line WISH is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis polyclonal targets IgG-Fc Fragment
View all literature mentions