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| 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
Other
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| 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.
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| 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.
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| Contributor(s) |
Lin L, Degn SE |
| Citation missing |
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| |
| Submission date |
May 06, 2022 |
| Last update date |
Jul 01, 2022 |
| Contact name |
Lin Lin |
| E-mail(s) |
lin.lin@biomed.au.dk
|
| Organization name |
Aarhus University
|
| Department |
Department of Biomedicine
|
| Street address |
Høegh-Guldbergs Gade 10
|
| City |
Aarhus |
| ZIP/Postal code |
8000 |
| Country |
Denmark |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL28457 |
DNBSEQ-G400 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA835703 |
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