Remodeling of colon plasma cell repertoire within ulcerative colitis patients
Name
jem_20220538.pdf
Description
Published version
Size
9.66 MB
Format
Adobe PDF
Checksum (MD5)
661c449eec1f26f2bce0e15555c4c38c
Author(s)
Scheid, Johannes F
Eraslan, Basak
Hudak, Andrew
Brown, Eric M
Sergio, Dallis
Delorey, Toni M
Phillips, Devan
Lefkovith, Ariel
Jess, Alison T
Duck, Lennard W
Date Issued
April 3, 2023
Journal
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Citation
Johannes F. Scheid, Basak Eraslan, Andrew Hudak, Eric M. Brown, Dallis Sergio, Toni M. Delorey, Devan Phillips, Ariel Lefkovith, Alison T. Jess, Lennard W. Duck, Charles O. Elson, Hera Vlamakis, Damian R. Plichta, Jacques Deguine, Ashwin N. Ananthakrishnan, Daniel B. Graham, Aviv Regev, Ramnik J. Xavier; Remodeling of colon plasma cell repertoire within ulcerative colitis patients. J Exp Med 3 April 2023; 220 (4): e20220538.
Version
Final published version
Abstract
Plasma cells (PCs) constitute a significant fraction of colonic mucosal cells and contribute to inflammatory infiltrates in ulcerative colitis (UC). While gut PCs secrete bacteria-targeting IgA antibodies, their role in UC pathogenesis is unknown. We performed single-cell V(D)J- and RNA-seq on sorted B cells from the colon of healthy individuals and patients with UC. A large fraction of B cell clones is shared between different colon regions, but inflammation in UC broadly disrupts this landscape, causing transcriptomic changes characterized by an increase in the unfolded protein response (UPR) and antigen presentation genes, clonal expansion, and isotype skewing from IgA1 and IgA2 to IgG1. We also directly expressed and assessed the specificity of 152 mAbs from expanded PC clones. These mAbs show low polyreactivity and autoreactivity and instead target both shared bacterial antigens and specific bacterial strains. Altogether, our results characterize the microbiome-specific colon PC response and how its disruption might contribute to inflammation in UC.
MIT Department
Broad Institute of MIT and Harvard
Klarman Cell Observatory (Broad Institute)
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-ShareAlike
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DOI of Published Version
https://doi.org/10.1084/jem.20220538
