Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity

Academic Article

Abstract

  • B 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.
  • Published In

  • Nature Medicine  Journal
  • Digital Object Identifier (doi)

    Author List

  • Uzzan M; Martin JC; Mesin L; Livanos AE; Castro-Dopico T; Huang R; Petralia F; Magri G; Kumar S; Zhao Q
  • Start Page

  • 766
  • End Page

  • 779
  • Volume

  • 28
  • Issue

  • 4