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Series GSE202358 Query DataSets for GSE202358
Status Public on Jul 01, 2022
Title Antigen presentation by B cells enables epitope spreading across an MHC barrier
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary A progressive increase in the breadth and specificity of autoantibodies over time, termed epitope spreading, drives pathogenic targeting of an ever-widening repertoire of self-components in many autoimmune diseases. Ostensibly, this progressive inclusion of additional B cell clones into an ongoing autoreactive response can occur through linked recognition, whereby proto-autoreactive B cells recognize distinct antigenic epitopes, which carry shared T cell epitopes. In a murine model displaying epitope spreading resembling that observed in systemic lupus erythematosus, we find that the epitope spreading process is compartmentalized by MHC. Antigen presentation by B cells carrying two MHC haplotypes can bridge the MHC barrier between two compartments of B cells that do not share MHC haplotypes, by communicating with two separate pools of MHC-restricted T cells. This leads to inclusion of distinct and diverse B cell reactivities in germinal centers. Our findings demonstrate a formidable capacity of B cells to drive the autoreactive response.
Overall design To better understand the immune landscape of the ‘no-bridge’ and ‘bridge’ chimeras, we leveraged the BD Rhapsody platform to perform linked single-cell Abseq, immune profiling and BCR/TCR analyses. We analyzed total splenocytes from two no-bridge chimeras, and total splenocytes enriched for GC B cells from a bridge chimera.
Contributor(s) Lin L, Degn SE
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Submission date May 06, 2022
Last update date Jul 01, 2022
Contact name Lin Lin
Organization name Aarhus University
Department Department of Biomedicine
Street address Høegh-Guldbergs Gade 10
City Aarhus
ZIP/Postal code 8000
Country Denmark
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL28457 DNBSEQ-G400 (Mus musculus)
Samples (18)
GSM6111883 1027_A_immune_panel
GSM6111884 1027_A_BCR_TCR
GSM6111885 1027_A_abseq
BioProject PRJNA835703

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Supplementary file Size Download File type/resource 1.0 Mb (ftp)(http) ZIP 833.3 Kb (ftp)(http) ZIP 1017.6 Kb (ftp)(http) ZIP 1006.1 Kb (ftp)(http) ZIP 1.1 Mb (ftp)(http) ZIP 1021.6 Kb (ftp)(http) ZIP 48.3 Kb (ftp)(http) ZIP
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