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Disease-specific B cell clones are shared between patients with Crohn’s disease

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Peer-reviewed

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Abstract

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.

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Acknowledgements: This work was funded by the Medical Research Council (Programme Grants MR/L019027/1 and MR/W018861/1). E.F.M. was supported by a Wellcome Trust (10406/Z/14/A and Beit Foundation (10406/Z/14/Z). K.G.C.S. was supported by a Wellcome Trust Senior Investigator award (200871/Z/16/Z). J.C.L. is a Lister Prize Fellow and is supported by the Francis Crick Institute, which receives core funding from Cancer Research UK (CC2219), the UK Medical Research Council (CC2219) and the Wellcome Trust (CC2219). P.K. is the recipient of a Jacquot Research Establishment Fellowship of the Royal Australasian College of Physicians Foundation, Fulbright Fellowship and NHMRC Investigator grant (2025210). L.W.U. is supported by the Erwin Schroedinger fellowship of the Austrian Science Fund (FWF J4396). We thank the Cambridge NIHR BRC Stratified Medicine Core Laboratory NGS Hub (supported by an MRC Clinical Infrastructure Award) for BCR sequencing. J.G. was supported by a Doris Duke Physician Scientist Fellowship Award (2021091), CZ Biohub Physician Scientist Scholar Award, NIH NIDDK LRP Award (2L30 DK126220), and a Stanford Maternal & Child Health Research Institute Pediatric IBD and Celiac Disease Research Award. We also thank Susanna Marquez from Yale University for help with implementing the Immcantation portal, Fan Yang from Stanford University for help with processing the post-mortem BCR datasets and Moira Finlay from the Royal Melbourne Hospital for help with histology. Graphical illustrations created with BioRender.com.

Journal Title

Nature Communications

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Journal ISSN

2041-1723
2041-1723

Volume Title

16

Publisher

Springer Science and Business Media LLC

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Except where otherwised noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Sponsorship
Medical Research Council (MR/L019027/1)
Wellcome Trust (200871/Z/16/Z)
Medical Research Council (MR/W018861/1)