Disease-specific B cell clones are shared between patients with Crohn’s disease
B cells have important functions in gut homeostasis, and dysregulated B cell populations are frequently observed in patients with inflammatory bowel diseases, including both ulcerative colitis (UC) and Crohn's disease (CD). How these B cell perturbations contribute to disease remains largely unknown. Here, we perform deep sequencing of the B cell receptor (BCR) repertoire in four cohorts of patients with CD, together with healthy controls and patients with UC. We identify BCR clones that are shared between patients with CD but not found in healthy individuals nor in patients with UC, indicating CD-associated B cell immune responses. Shared clones are present in the inflamed gut mucosa, draining intestinal lymph nodes and blood, suggesting the presence of common CD-associated antigens that drive B cell responses in CD patients.
Authors
- Kenneth G. C. Smith (ORCID: https://orcid.org/0000-0003-3829-4326)
- Sofie H. Tolmeijer (ORCID: https://orcid.org/0000-0003-4066-885X)
- Prasanti Kotagiri (ORCID: https://orcid.org/0000-0002-9806-4349)
- Eoin McKinney (ORCID: https://orcid.org/0000-0003-3516-3072)
- William Rae (ORCID: https://orcid.org/0000-0003-0095-2514)
- Rachael Bashford-Rogers (ORCID: https://orcid.org/0000-0002-6838-0711)
- Nurulamin M Noor (ORCID: https://orcid.org/0000-0003-3426-6408)
- Paul Lyons (ORCID: https://orcid.org/0000-0001-7035-8997)
- Ji-Yeun Lee (ORCID: https://orcid.org/0000-0002-0463-6802)
- Lukas Unger (ORCID: https://orcid.org/0000-0002-8423-2268)
- David Bingham (ORCID: https://orcid.org/0000-0002-3368-1549)
- Scott D. Boyd (ORCID: https://orcid.org/0000-0003-0963-044X)
- John Gubatan (ORCID: https://orcid.org/0000-0001-6037-2883)
- Giulia Manferrari (ORCID: https://orcid.org/0000-0001-7062-1142)
- Stephan Rogalla (ORCID: https://orcid.org/0000-0002-1311-2672)
- Diana Pombal
- Raoul S. Sojwal (ORCID: https://orcid.org/0000-0002-1424-1505)
- Laura Bergamaschi (ORCID: https://orcid.org/0000-0002-2537-8603)
- Samuel J. S. Rubin (ORCID: https://orcid.org/0000-0001-7335-3868)
- Anton Stift (ORCID: https://orcid.org/0000-0002-7243-8138)
- James Christopher Lee (ORCID: https://orcid.org/0000-0001-5711-9385)
Institutions
- AstraZeneca (United Kingdom) (GB)
- University of Cambridge (GB)
- The Francis Crick Institute (GB)
- University of Oxford (GB)
- Cambridge School (PT)
- AstraZeneca (Singapore) (SG)
- MRC Epidemiology Unit (GB)
- AstraZeneca (Germany) (DE)
- University College London (GB)
- Monash University (AU)
- Medical University of Vienna (AT)
- Stanford University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-17
- DOI
- https://doi.org/10.1038/s41467-025-58977-y
- Citations
- 8
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 6.38
Funders
- Yale University
- Wellcome Trust
- Francis Crick Institute
- Cancer Research UK
- National Institute for Health and Care Research
- Austrian Science Fund
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases
- Medical Research Foundation