期刊
NATURE COMMUNICATIONS
卷 3, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms1769
关键词
-
资金
- NIH [AI 045011, AI 079705, AI 060573]
By diversifying antibody biological effector functions, class switch DNA recombination has a central role in the maturation of the antibody response. Here we show that BCR-signalling synergizes with Toll-like receptor (TLR) signalling to induce class switch DNA recombination. BCR-signalling activates the non-canonical NF-kappa B pathway and enhances the TLR-dependent canonical NF-kappa B pathway, thereby inducing activation-induced cytidine deaminase (AID), which is critical for class switch DNA recombination. Escherichia coli lipopolysaccharide (LPS) triggers dual TLR4/BCR-signalling and induces hallmarks of BCR-signalling, including CD79a phosphorylation and Ca2+ mobilization, and activates both the NF-kappa B pathways to induce AID and class switch DNA recombination in a PI(3) K p85 alpha-dependent fashion. CD40-signalling activates the two NF-kappa B pathways to induce AID and class switch DNA recombination independent of BCR-signalling. Finally, dual BCR/TLR-engaging NP-lipopolysaccharide effectively elicits class-switched NP-specific IgG3 and IgG2b in mice. Thus, by integrating signals of the non-canonical and canonical NF-kappa B pathways, BCR and TLRs synergize to induce AID and T-cell-independent class switch DNA recombination.
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