T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells.
Immunity
; 29(2): 249-60, 2008 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-18691914
ABSTRACT
On the lupus-prone MRL-lpr/lpr (MRL-lpr) background, AM14 rheumatoid factor (RF) B cells are activated, differentiate into plasmablasts, and undergo somatic hypermutation outside of follicles. Using multiple strategies to impair T cells, we found that such AM14 B cell activation did not require T cells but could be modulated by them. In vitro, the signaling adaptor MyD88 is required for IgG anti-chromatin to stimulate AM14 B cell proliferation when T cells are absent. However, the roles of Toll-like receptors (TLRs) in AM14 B cell activation in vivo have not been investigated. We found that activation, expansion, and differentiation of AM14 B cells depended on MyD88; however, mice lacking either TLR7 or TLR9 displayed partial defects, indicating complex roles for these receptors. T cell-independent activation of certain autoreactive B cells, which gain stimuli via endogenous TLR ligands instead of T cells, may be the initial step in the generation of canonical autoantibodies.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article