Increased positive selection of B1 cells and reduced B cell tolerance to intracellular antigens in c1q-deficient mice.
J Immunol
; 178(5): 2916-22, 2007 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-17312136
ABSTRACT
Inherited deficiency of early components of the classical complement pathway is strongly associated with the targeting of intracellular self Ags in systemic lupus erythematosus, but the reasons for this association are debated. In this study, we show that C1q deficiency increases the positive selection of B1b B cells and IgM autoantibodies by an intracellular self Ag, which is exposed on dying cells, and decreases the negative selection of autoreactive conventional B cells by the same Ag. These effects are specific to intracellular Ag because C1q deficiency does not affect negative selection by extracellular self Ag or increase the positive selection of naive B cells. The B1-derived IgM autoantibody binds to the intracellular Ag when it is expressed on dying cells, leading to fixation of C1q and clearance of cells by phagocytosis. These findings suggest that the positive selection of autoreactive B1 cells by self Ags may contribute to the IgM and C1q-dependent clearance of dying cells in a feedback loop that limits exposure of conventional B cells to immunogenic self Ags. We show that exposure of intracellular Ag leads to the activation of conventional B cells, when there is a source of T cell help in vivo.
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Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Linfócitos B
/
Ativação Linfocitária
/
Complemento C1q
/
Tolerância Imunológica
/
Lúpus Eritematoso Sistêmico
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2007
Tipo de documento:
Article