Open AccessLongevity, clonal relationship, and transcriptional program of celiac disease–specific plasma cells
Author(s) -
Ida Lindeman,
Chunyan Zhou,
Linn M Eggesbø,
Zhichao Miao,
Justyna Polak,
Knut E.A. Lundin,
Jørgen Jahnsen,
ShuoWang Qiao,
Rasmus Iversen,
Ludvig M. Sollid
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20200852
Subject(s) - biology , antibody , tissue transglutaminase , antigen , disease , pathogenesis , immunology , population , gene , genetics , microbiology and biotechnology , medicine , enzyme , environmental health , biochemistry
Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGPs) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls and performed RNA sequencing with clonal inference and transcriptomic analysis of 3,251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific and non–disease-specific PCs and between short-lived and long-lived PCs. The short-lived CD19+CD45+ phenotype dominated in untreated and short-term–treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens.