Elimination of germinal-center-derived self-reactive B cells is governed by the location and concentration of self-antigen.
Immunity
; 37(5): 893-904, 2012 Nov 16.
Article
em En
| MEDLINE
| ID: mdl-23142780
ABSTRACT
Secondary diversification of the B cell repertoire by immunoglobulin gene somatic hypermutation in the germinal center (GC) is essential for providing the high-affinity antibody specificities required for long-term humoral immunity. While the risk to self-tolerance posed by inadvertent generation of self-reactive GC B cells has long been recognized, it has not previously been possible to identify such cells and study their fate. In the current study, self-reactive B cells generated de novo in the GC failed to survive when their target self-antigen was either expressed ubiquitously or specifically in cells proximal to the GC microenvironment. By contrast, GC B cells that recognized rare or tissue-specific self-antigens were not eliminated, and could instead undergo positive selection by cross-reactive foreign antigen and produce plasma cells secreting high-affinity autoantibodies. These findings demonstrate the incomplete nature of GC self-tolerance and may explain the frequent association of cross-reactive, organ-specific autoantibodies with postinfectious autoimmune disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Linfócitos B
/
Centro Germinativo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Immunity
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Austrália