NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE133028 Query DataSets for GSE133028
Status Public on Aug 31, 2020
Title CSF B cells in relapsing multiple sclerosis are driven towards an antigen-experienced, inflammatory fate
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Central nervous system B cells have several potential roles in multiple sclerosis (MS): secretors of proinflammatory cytokines and chemokines, presenters of autoantigens to T cells, producers of pathogenic antibodies, and reservoirs for viruses that trigger demyelination. To interrogate these roles, single-cell RNA sequencing (scRNA-Seq) was performed on paired cerebrospinal fluid (CSF) and blood from subjects with relapsing-remitting MS (RRMS; n = 12), other neurologic diseases (ONDs; n = 1), and healthy controls (HCs; n = 3). Single-cell immunoglobulin sequencing (scIg-Seq) was performed on a subset of these subjects and additional RRMS (n = 4), clinically isolated syndrome (n = 2), and OND (n = 2) subjects. Further, paired CSF and blood B cell subsets (RRMS; n = 7) were isolated using fluorescence activated cell sorting for bulk RNA sequencing (RNA-Seq). Independent analyses across technologies demonstrated that nuclear factor kappa B (NF-?B) and cholesterol biosynthesis pathways were activated, and specific cytokine and chemokine receptors were up-regulated in CSF memory B cells. Further, SMAD/TGF-ß1 signaling was down-regulated in CSF plasmablasts/plasma cells. Clonally expanded, somatically hypermutated IgM+ and IgG1+ CSF B cells were associated with inflammation, blood–brain barrier breakdown, and intrathecal Ig synthesis. While we identified memory B cells and plasmablast/plasma cells with highly similar Ig heavy-chain sequences across MS subjects, similarities were also identified with ONDs and HCs. No viral transcripts, including from Epstein–Barr virus, were detected. Our findings support the hypothesis that in MS, CSF B cells are driven to an inflammatory and clonally expanded memory and plasmablast/plasma cell phenotype.
 
Overall design 5' or 3' Single-cell RNA sequencing was performed on the CSF and blood for a cohort of relapsing MS patients, patients with other neurologic diseases, and healthy controls. 5' Single-cell immunoglobulin sequencing was performed on a subset of these subjects and additional subjects with relapsing MS, clinically isolated syndrome, and patients with other neurologic diseases. Additionally, total RNA from 10 B cell subsets (5 Blood and 5 CSF) from a separate cohort of relapsing MS patients were sorted using FACS and sequenced using bulk RNA sequencing.
 
Contributor(s) Ramesh A, Schubert RD, Greenfield AL, Dandekar R, Loudermilk R, Sabatino JJ, Koelzer MT, Tran EB, Koshal K, Kim K, Pröbstel A, Banerji D, Guo C, Green AJ, Bove RM, DeRisi JL, Gelfand JM, Cree BC, Zamvil SS, Baranzini SE, Hauser SL, Wilson MR
Citation(s) 32859762
Submission date Jun 19, 2019
Last update date Apr 28, 2021
Contact name Akshaya Ramesh
E-mail(s) akshaya.rameshv@gmail.com
Organization name UCSF
Street address 675 Nelson Rising Lane
City San Francisco
ZIP/Postal code 94158
Country USA
 
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL27644 Illumina Novaseq 6000 (Homo sapiens)
Samples (98)
GSM3898576 Patient 2 IgD-CD27- double negative B cells from the CSF
GSM3898577 Patient 2 IgD+CD27- naïve B cells from the CSF
GSM3898578 Patient 2 IgD-CD27++ plasmablasts/plasma cells B cells from the CSF
Relations
BioProject PRJNA549712
SRA SRP201915

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE133028_RAW.tar 292.8 Mb (http)(custom) TAR (of CSV, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap