Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity
Updated February 24, 2023B cells, which are critical for intestinal homeostasis, remain understudied in ulcerative colitis (UC). In this study, we recruited three cohorts of patients with UC (primary cohort, n = 145; validation cohort 1, n = 664; and validation cohort 2, n = 143) to comprehensively define the landscape of B cells during UC-associated intestinal inflammation. Using single-cell RNA sequencing, single-cell IgH gene sequencing and protein-level validation, we mapped the compositional, transcriptional and clonotypic landscape of mucosal and circulating B cells. We found major perturbations within the mucosal B cell compartment, including an expansion of naive B cells and IgG+ plasma cells with curtailed diversity and maturation. Furthermore, we isolated an auto-reactive plasma cell clone targeting integrin αvβ6 from inflamed UC intestines. We also identified a subset of intestinal CXCL13-expressing TFH-like T peripheral helper cells that were associated with the pathogenic B cell response. Finally, across all three cohorts, we confirmed that changes in intestinal humoral immunity are reflected in circulation by the expansion of gut-homing plasmablasts that correlates with disease activity and predicts disease complications. Our data demonstrate a highly dysregulated B cell response in UC and highlight a potential role of B cells in disease pathogenesis.
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Analysis Portals
NoneProject Label
Mehandru-Human-10x3pv2Species
Sample Type
Anatomical Entity
Organ Part
Selected Cell Types
Disease Status (Specimen)
Disease Status (Donor)
Development Stage
Library Construction Method
Nucleic Acid Source
Paired End
falseAnalysis Protocol
analysis_protocol_1File Format
Cell Count Estimate
40.3kDonor Count
9