Back to Search
Start Over
Generation of circulating autoreactive pre-plasma cells fueled by naive B cells in celiac disease
- Source :
- Cell Reports; April 2024, Vol. 43 Issue: 4
- Publication Year :
- 2024
-
Abstract
- Autoantibodies against the enzyme transglutaminase 2 (TG2) are characteristic of celiac disease (CeD), and TG2-specific immunoglobulin (Ig) A plasma cells are abundant in gut biopsies of patients. Here, we describe the corresponding population of autoreactive B cells in blood. Circulating TG2-specific IgA cells are present in untreated patients on a gluten-containing diet but not in controls. They are clonally related to TG2-specific small intestinal plasma cells, and they express gut-homing molecules, indicating that they are plasma cell precursors. Unlike other IgA-switched cells, the TG2-specific cells are negative for CD27, placing them in the double-negative (IgD−CD27−) category. They have a plasmablast or activated memory B cell phenotype, and they harbor fewer variable region mutations than other IgA cells. Based on their similarity to naive B cells, we propose that autoreactive IgA cells in CeD are generated mainly through chronic recruitment of naive B cells via an extrafollicular response involving gluten-specific CD4+T cells.
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 43
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Cell Reports
- Publication Type :
- Periodical
- Accession number :
- ejs65833882
- Full Text :
- https://doi.org/10.1016/j.celrep.2024.114045