Selective activation of naïve B cells with unique epitope specificity shapes autoantibody formation in celiac disease.
J Autoimmun
; 146: 103241, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38754235
ABSTRACT
Many antibody responses induced by infection, vaccination or autoimmunity show signs of convergence across individuals with epitope-dependent selection of particular variable region gene segments and complementarity determining region 3 properties. However, not much is known about the relationship between antigen-specific effector cells and antigen-specific precursors present in the naïve B-cell repertoire. Here, we sought to address this relationship in the context of celiac disease, where there is a stereotyped autoantibody response against the enzyme transglutaminase 2 (TG2). By generating TG2-specific monoclonal antibodies from both duodenal plasma cells and circulating naïve B cells, we demonstrate a discord between the naïve TG2-specific repertoire and the cells that are selected for autoantibody production. Hence, the naïve repertoire does not fully reflect the epitope preference and gene usage observed for memory B cells and plasma cells. Instead, distinct naïve B cells that target particular TG2 epitopes appear to be selectively activated at the expense of TG2-binding B cells targeting other epitopes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Linfócitos B
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Ativação Linfocitária
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Doença Celíaca
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Transglutaminases
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Epitopos de Linfócito B
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Proteínas de Ligação ao GTP
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Proteína 2 Glutamina gama-Glutamiltransferase
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Autoimmun
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Noruega