biostudies-literatureScheid JFNIDDK NIH HHSCrohn's and Colitis FoundationNational Institutes of HealthKlarman Cell Observatorye20220538https://www.ebi.ac.uk/biostudies/studies/S-EPMC9949229biostudies-literatureUnknown220(4)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 mThe Journal of experimental medicineRemodeling of colon plasma cell repertoire within ulcerative colitis patients.PMC9949229RC2 DK114784P30 DK043351Duck LWVlamakis HXavier RJEraslan BSergio DScheid JFBrown EMPlichta DRDeguine JHudak ADelorey TMRegev ALefkovith AJess ATPhillips DAnanthakrishnan ANGraham DBElson COfalseRemodeling of colon plasma cell repertoire within ulcerative colitis patients.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 m2023-01-01T00:00:00Z2023 Apr2025-04-04T20:04:05.932Z2025-04-04T20:04:05.932ZS-EPMC99492293675279710.1084/jem.20220538