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J Autoimmun ; 146: 103241, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754235

RESUMO

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.


Assuntos
Autoanticorpos , Linfócitos B , Doença Celíaca , Epitopos de Linfócito B , Proteínas de Ligação ao GTP , Ativação Linfocitária , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases , Doença Celíaca/imunologia , Humanos , Autoanticorpos/imunologia , Transglutaminases/imunologia , Epitopos de Linfócito B/imunologia , Proteínas de Ligação ao GTP/imunologia , Ativação Linfocitária/imunologia , Linfócitos B/imunologia , Plasmócitos/imunologia , Plasmócitos/metabolismo , Feminino , Anticorpos Monoclonais/imunologia , Epitopos/imunologia , Masculino , Adulto , Duodeno/imunologia , Duodeno/patologia
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