B cell antigen receptor-induced activation of an IRAK4-dependent signaling pathway revealed by a MALT1-IRAK4 double knockout mouse model

11.03.2011

Dufner A, Schamel WW

Cell Commun Signal. 2011;9(1):6

In this BIOSS publication we identify a novel cross-talk between the B cell antigen receptor (BCR) and the pathogen recognition receptor TLR4 pathways in B cell activation on the level of the kinases IRAK1 and IRAK4. The BCR activates the transcription factor nuclear factor-kB (NF-kB) via recruitment of CARD11, BCL10 and MALT1 into lipid rafts. The activation strictly depends on BCL10, but not on MALT1, sugessting that a MALT1-independent NF-kB activation pathway contributes to BCR-induced NF-kB activation downstream of BCL10.
Using B cells from knock out mice as well as biochemical analyses, we demonstrate in this work that the IRAK4- and IRAK1-dependent TLR4 signaling branch is activated by the BCR to induce NF-kB activation. In fact, BCR-induced MALT1-independent IkB degradation and B cell proliferation were inhibited in MALT1/IRAK4 double knockout B cells. Likewise, IRAK1 was recruited into lipid rafts upon BCR stimulation and activated following recruitment of IRAK4.
The novel crosstalk between BCR and TLR signaling components may contribute to the discrimination of signals that emanate from single and dual receptor engagement to control adaptive B cell responses.