BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NFKB pathway

(a) BCR crosslinking activates the non-canonical NF-κB pathway by inducing expression of p100 and its processing to p52 in a PI(3)K-dependent fashion. TLR engagement (as exemplified by TLR4 engagement by lipid A) activates the canonical NF-κB pathway, resulting in limited Aicda expression and marginal CSR. BCR enhances the TLR-dependent canonical NF-κB pathway, likely through TRAF6 activation, and TLR enhances the BCR-activated non-canonical NF-κB pathway by inducing p100 expression, thereby synergizing in inducing AID and CSR. (b) Unlike lipid A, LPS triggers both BCR-signalling through its polysaccharidic moiety and TLR4-signalling through its lipid A moiety, thereby activating both the non-canonical and canonical NF-κB pathways to induce AID and CSR in a PI(3)K-dependent fashion. (c) CD40 activation of the non-canonical and canonical NF-κB pathways and induction of CSR depend on TRAF2/TRAF3, which, however, play no role in the BCR-signalling pathway; TRAF6 mediates activation of the canonical NF-κB pathway only and is dispensable for CSR induced by CD40-signalling.

Publication

BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway. (2012) Egest J. Pone, et al. Nat Commun. 2012 Apr 3;3:767. Figure: F8. All organisms Capra hircus Rattus norvegicus Mus musculus Homo sapiens Danio rerio

Disease mentions