Generation of circulating autoreactive pre-plasma cells fueled by naive B cells in celiac disease.
Cell Rep
; 43(4): 114045, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38578826
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plasmócitos
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Imunoglobulina A
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Linfócitos B
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Doença Celíaca
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Transglutaminases
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Proteínas de Ligação ao GTP
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Proteína 2 Glutamina gama-Glutamiltransferase
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article