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T Cell-Independent and Toll-like Receptor-Dependent Antigen-Driven Activation of Autoreactive B Cells

2008; Cell Press; Volume: 29; Issue: 2 Linguagem: Inglês

10.1016/j.immuni.2008.06.009

1097-4180

Robin Herlands, Sean R. Christensen, Rebecca A. Sweet, Uri Hershberg, Mark J. Shlomchik,

T-cell and B-cell Immunology

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.