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" BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway. "
Pone, Egest J; Zhang, Jinsong; Mai, Thach; White, Clayton A; Li, Guideng; Sakakura, John K; Patel, Pina J; Al-Qahtani, Ahmed; Zan, Hong; Xu, Zhenming; Casali, Paolo
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AL
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| Record Number
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909530
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LA7w8124r7
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| Title & Author
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BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway. [Article]\ Pone, Egest J; Zhang, Jinsong; Mai, Thach; White, Clayton A; Li, Guideng; Sakakura, John K; Patel, Pina J; Al-Qahtani, Ahmed; Zan, Hong; Xu, Zhenming; Casali, Paolo
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2012
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| Title of Periodical
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UC Irvine
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| Abstract
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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-κB pathway and enhances the TLR-dependent canonical NF-κB 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 Ca(2+) mobilization, and activates both the NF-κB pathways to induce AID and class switch DNA recombination in a PI(3)K p85α-dependent fashion. CD40-signalling activates the two NF-κB 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-κB pathways, BCR and TLRs synergize to induce AID and T-cell-independent class switch DNA recombination.
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