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

BACKGROUND: The B cell antigen receptor (BCR) and pathogen recognition receptors, such as Toll-like receptor 4 (TLR4), act in concert to control adaptive B cell responses. However, little is known about the signaling pathways that integrate BCR activation with intrinsic TLR4 stimulation. Antigen rec...

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Detalles Bibliográficos
Autores principales: Dufner, Almut, Schamel, Wolfgang W
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061960/
https://www.ncbi.nlm.nih.gov/pubmed/21396111
http://dx.doi.org/10.1186/1478-811X-9-6
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author Dufner, Almut
Schamel, Wolfgang W
author_facet Dufner, Almut
Schamel, Wolfgang W
author_sort Dufner, Almut
collection PubMed
description BACKGROUND: The B cell antigen receptor (BCR) and pathogen recognition receptors, such as Toll-like receptor 4 (TLR4), act in concert to control adaptive B cell responses. However, little is known about the signaling pathways that integrate BCR activation with intrinsic TLR4 stimulation. Antigen receptors initialize activation of the inducible transcription factor nuclear factor-κB (NF-κB) via recruitment of the membrane-associated guanylate kinase caspase recruitment domain protein 11 (CARD11), the adapter molecule B cell CLL/lymphoma 10 (BCL10), and the "paracaspase" mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) into lipid rafts. Upon BCR triggering, this activation strictly depends on BCL10, but not on MALT1, leading to the hypothesis that a MALT1-independent NF-κB activation pathway contributes to BCR-induced NF-κB activation downstream of BCL10. The identity of this pathway has remained elusive. RESULTS: Using genetic and biochemical approaches, we demonstrate that the IRAK4- and IRAK1-dependent TLR signaling branch is activated upon BCR triggering to induce partial NF-κB activation. BCR-induced MALT1-independent IκB degradation and B cell proliferation were inhibited in MALT1/IRAK4 double knockout B cells. Moreover, IRAK1 was recruited into lipid rafts upon BCR stimulation and activated following transient recruitment of IRAK4. CONCLUSION: We propose that the observed 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.
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spelling pubmed-30619602011-03-22 B cell antigen receptor-induced activation of an IRAK4-dependent signaling pathway revealed by a MALT1-IRAK4 double knockout mouse model Dufner, Almut Schamel, Wolfgang W Cell Commun Signal Research BACKGROUND: The B cell antigen receptor (BCR) and pathogen recognition receptors, such as Toll-like receptor 4 (TLR4), act in concert to control adaptive B cell responses. However, little is known about the signaling pathways that integrate BCR activation with intrinsic TLR4 stimulation. Antigen receptors initialize activation of the inducible transcription factor nuclear factor-κB (NF-κB) via recruitment of the membrane-associated guanylate kinase caspase recruitment domain protein 11 (CARD11), the adapter molecule B cell CLL/lymphoma 10 (BCL10), and the "paracaspase" mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) into lipid rafts. Upon BCR triggering, this activation strictly depends on BCL10, but not on MALT1, leading to the hypothesis that a MALT1-independent NF-κB activation pathway contributes to BCR-induced NF-κB activation downstream of BCL10. The identity of this pathway has remained elusive. RESULTS: Using genetic and biochemical approaches, we demonstrate that the IRAK4- and IRAK1-dependent TLR signaling branch is activated upon BCR triggering to induce partial NF-κB activation. BCR-induced MALT1-independent IκB degradation and B cell proliferation were inhibited in MALT1/IRAK4 double knockout B cells. Moreover, IRAK1 was recruited into lipid rafts upon BCR stimulation and activated following transient recruitment of IRAK4. CONCLUSION: We propose that the observed 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. BioMed Central 2011-03-11 /pmc/articles/PMC3061960/ /pubmed/21396111 http://dx.doi.org/10.1186/1478-811X-9-6 Text en Copyright ©2011 Dufner and Schamel; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Dufner, Almut
Schamel, Wolfgang W
B cell antigen receptor-induced activation of an IRAK4-dependent signaling pathway revealed by a MALT1-IRAK4 double knockout mouse model
title B cell antigen receptor-induced activation of an IRAK4-dependent signaling pathway revealed by a MALT1-IRAK4 double knockout mouse model
title_full B cell antigen receptor-induced activation of an IRAK4-dependent signaling pathway revealed by a MALT1-IRAK4 double knockout mouse model
title_fullStr B cell antigen receptor-induced activation of an IRAK4-dependent signaling pathway revealed by a MALT1-IRAK4 double knockout mouse model
title_full_unstemmed B cell antigen receptor-induced activation of an IRAK4-dependent signaling pathway revealed by a MALT1-IRAK4 double knockout mouse model
title_short B cell antigen receptor-induced activation of an IRAK4-dependent signaling pathway revealed by a MALT1-IRAK4 double knockout mouse model
title_sort b cell antigen receptor-induced activation of an irak4-dependent signaling pathway revealed by a malt1-irak4 double knockout mouse model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061960/
https://www.ncbi.nlm.nih.gov/pubmed/21396111
http://dx.doi.org/10.1186/1478-811X-9-6
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