Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus.

Scott A Jenks | Kevin S Cashman | Esther Zumaquero | Urko M Marigorta | Aakash V Patel | Xiaoqian Wang | Deepak Tomar | Matthew C Woodruff | Zoe Simon | Regina Bugrovsky | Emily L Blalock | Christopher D Scharer | Christopher M Tipton | Chungwen Wei | S Sam Lim | Michelle Petri | Timothy B Niewold | Jennifer H Anolik | Greg Gibson | F Eun-Hyung Lee | Jeremy M Boss | Frances E Lund | Ignacio Sanz
Immunity | 2018

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

Antibodies used in this publication

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R37 AI049660
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI109962
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI121252
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI125180
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI110508
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI078907
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK007656
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI123733
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR069572
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI110483

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.

This is a list of tools and resources that we have found mentioned in this publication.


SAM format (tool)

RRID:SCR_012093

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 mentions

edgeR (tool)

RRID:SCR_012802

Bioconductor 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 mentions

Bethyl (tool)

RRID:SCR_013554

An Antibody supplier

View all literature mentions

SARTools (tool)

RRID:SCR_016533

Software package as a DESeq2- and EdgeR-Based R Pipeline for Comprehensive Differential Analysis of RNA-Seq Data.

View all literature mentions

Alexa Fluor(R) 488 anti-IRF4 (antibody)

RRID:AB_2563266

This monoclonal targets IRF4

View all literature mentions

Purified anti-T-bet (antibody)

RRID:AB_1595608

This monoclonal targets T-bet

View all literature mentions

PE anti-human CD307d (FcRL4) (antibody)

RRID:AB_1575103

This monoclonal targets CD307d

View all literature mentions

IgG (antibody)

RRID:AB_2738986

This monoclonal targets IgG

View all literature mentions

CD20 (cytoplasmic) (antibody)

RRID:AB_2738150

This monoclonal targets CD20 (cytoplasmic)

View all literature mentions

CD138 (antibody)

RRID:AB_400212

This monoclonal targets CD138

View all literature mentions

BLNK (pY84) (antibody)

RRID:AB_647182

This unknown targets BLNK, phospho (Tyr84)

View all literature mentions

PE anti-human CD319 (CRACC) (antibody)

RRID:AB_2239190

This monoclonal targets CD319

View all literature mentions

p38 MAPK (antibody)

RRID:AB_10896152

This monoclonal targets p38 MAPK

View all literature mentions

ChromPure Human IgG, whole molecule (antibody)

RRID:AB_2337043

This unknown targets Human IgG, whole molecule

View all literature mentions

IgD (antibody)

RRID:AB_396113

This monoclonal targets IgD

View all literature mentions

CD27 (antibody)

RRID:AB_2744351

This monoclonal targets CD27

View all literature mentions

PE anti-human CD307e (FcRL5) (antibody)

RRID:AB_2104588

This monoclonal targets CD307e

View all literature mentions

Human CXCR5 Allophycocyanin MAb (Clone 51505) (antibody)

RRID:AB_357109

This monoclonal targets Human CXCR5 Allophycocyanin MAb (Clone 51505)

View all literature mentions

HLA-DR (antibody)

RRID:AB_2739425

This monoclonal targets HLA-DR

View all literature mentions

CD27 (antibody)

RRID:AB_2738042

This monoclonal targets CD27

View all literature mentions

IgD (antibody)

RRID:AB_2738435

This monoclonal targets IgD

View all literature mentions

CD138-PE, human (antibody)

RRID:AB_244212

This monoclonal targets CD138

View all literature mentions

CD22 (antibody)

RRID:AB_395818

This monoclonal targets CD22

View all literature mentions

ERK1/2 (pT202/pY204) (antibody)

RRID:AB_10895978

This monoclonal targets ERK1/2 (pT202/pY204)

View all literature mentions

FlowJo (software resource)

RRID:SCR_008520

Software 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 mentions

Cytobank (web application)

RRID:SCR_014043

A 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 mentions

TopHat (software resource)

RRID:SCR_013035

Software 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 mentions

WISH (cell line)

RRID:CVCL_1909

Cell line WISH is a Cancer cell line with a species of origin Homo sapiens

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical 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 mentions

SAMTOOLS (software resource)

RRID:SCR_002105

Original 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 mentions