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Series GSE141117 Query DataSets for GSE141117
Status Public on Dec 31, 2019
Title An agonistic anti-CD137 antibody promotes inflammatory signatures in immune cells that disrupt germinal center formation and T cell-dependent antibody responses II
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary CD137 is a costimulatory receptor expressed on natural killer cells, T cells, and subsets of dendritic cells. An agonistic monoclonal antibody (mAb) against CD137 has been used to reduce tumor burden or reverse autoimmunity in animal models and clinical trials. When testing the ability of agonistic anti-CD137 mAb to promote clearance of persistent virus infection, we recently reported reduced numbers of germinal center B (GC B) cells and follicular dendritic cells (FDC) in lymphoid tissues. Here, we show that agonistic anti-CD137 agonistic mAb treatment impairs antibody responses with multiple T cell-dependent antigens including virus infection, recombinant viral antigens, and conjugated haptens but not with a T cell-independent antigen or at homeostasis. These effects were not due to enhanced apoptosis or impaired proliferation of B cells but instead correlated with disorganization of the stromal cell compartment of the GC, and were mediated by CD137 signaling in CD4+ and CD8+ T cells. Anti-CD137 treatment in the context of acute infection also resulted in reduced numbers of marginal zone B cells, greater numbers of antibody-secreting plasmablasts, and pro-inflammatory signatures in several myeloid and lymphoid cell populations of the spleen. Our experiments in mice suggest that agonistic anti-CD137 mAbs used in cancer and autoimmunity therapy may alter stromal cell populations to causes GC collapse and impaired long-term antibody and B cell memory responses.
 
Overall design Droplet-based 5′ end massively parallel single-cell RNA sequencing was performed by isolating single cells from mouse spleen after collagenase digestion, and libraries were prepared using Chromium Single Cell 5′ Reagent Kits in a BSL-3 level laboratory according to manufacturer’s protocol (10x Genomics). For B Cell repertoire libraries, amplified cDNA underwent two rounds of Target Enrichment using nested primer pairs specific for mouse B cell Ig constant regions. The generated scRNAseq libraries were sequenced a NovaSeq S4 flow cell.
Splenocytes from 3 biologically independent mice were pooled per sample.
 
Contributor(s) Hong JP, Reynoso G, Andhey PS, Swain A, Turner J, Boon AC, Krammer F, Ellebedy A, Zanini F, Artyomov M, Hickman HD, Diamond MS
Citation(s) 32699843
Submission date Nov 27, 2019
Last update date Jan 25, 2021
Contact name Maxim N. Artyomov
E-mail(s) martyomov@pathology.wustl.edu
Organization name Washington University in St.Louis
Department Immunology&Pathology
Street address 660 S. Euclid Avenue, Campus Box 8118
City St.Louis
State/province MO
ZIP/Postal code 63110
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (3)
GSM4195233 Naïve_BCR
GSM4195234 Isotype_7dpi_BCR
GSM4195235 Anti-CD137_7dpi_BCR
Relations
BioProject PRJNA592161
SRA SRP233498

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Supplementary file Size Download File type/resource
GSE141117_RAW.tar 6.5 Mb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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