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| Status |
Public on Aug 24, 2021 |
| Title |
Ulcerative Colitis is characterized by an intense and plasmablast skewed humoral response that associates with treatment resistance and disease complications |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
B cells, critical for intestinal homeostasis, remain under-studied in ulcerative colitis (UC). Using single-cell RNA sequencing, single cell IgH gene sequencing, and protein-level validation across three large UC cohorts, we mapped the cellular and clonotypic landscape of mucosal and circulating B cells in UC. We found major perturbations within the mucosal B cell compartment, including an expansion of naïve B cells and IgG+ plasma cells (PC) with curtailed diversity and maturation. Furthermore, we isolated an autoreactive plasma cell clone from inflamed UC intestines. We also identified a subset of intestinal CXCL13-expressing T follicular helper cells that were associated with the pathogenic B cell response. Finally, across three distinct cohorts, we confirmed that changes in intestinal humoral immunity are reflected in circulation by the expansion of gut-homing plasmablasts that associate with disease activity and predict disease complications. Our data demonstrate a highly dysregulated B cell response in UC and revisit the role of B cells in disease pathogenesis.
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| Overall design |
Single cell RNA sequencing was performed on cells extracted from colonic biopsies of inflamed mucosa (ulcerative colitis patients, n=5) and normal colonic mucosa (healthy controls, n=4)
Please note that sample titles have been updated on Sep 21, 2021.
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| Contributor(s) |
Kenigsberg E, Martin JC, Mehandru S, Uzzan M |
| Citation(s) |
35190725 |
| Submission date |
Aug 17, 2021 |
| Last update date |
Mar 25, 2022 |
| Contact name |
Darwin D'Souza |
| Organization name |
Human Immune Monitoring Center
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| Department |
ImmunoBio
|
| Street address |
1470 Madison Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA755629 |
| SRA |
SRP332901 |
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