TY - JOUR
T1 - The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88
AU - He, Bing
AU - Santamaria, Raul
AU - Xu, Weifeng
AU - Cols, Montserrat
AU - Chen, Kang
AU - Puga, Irene
AU - Shan, Meimei
AU - Xiong, Huabao
AU - Bussel, James B.
AU - Chiu, April
AU - Puel, Anne
AU - Reichenbach, Jeanine
AU - Marodi, László
AU - Döffinger, Rainer
AU - Vasconcelos, Julia
AU - Issekutz, Andrew
AU - Krause, Jens
AU - Davies, Graham
AU - Li, Xiaoxia
AU - Grimbacher, Bodo
AU - Plebani, Alessandro
AU - Meffre, Eric
AU - Picard, Capucine
AU - Cunningham-Rundles, Charlotte
AU - Casanova, Jean Laurent
AU - Cerutti, Andrea
N1 - Funding Information:
We thank S.Y. Zhang (University Paris Descartes) for peripheral blood mononuclear cells from patients deficient in the transmembrane protein Unc93b; S. Vogel and A. Medvedev (University of Maryland) for DN-IRAK4-C877T; J.D. Li (University of South California) for DN-IKKα(K44M) and DN-IKKβ(K49A); J. Jun Ninomiya-Tsuji (Lerner Research Institute) for DN-TAK1(K63W); Z. Cao (Tularik) for DN-IRAK1 (1–208); and the Mount Sinai School of Medicine Microscopy Shared Resource Facility. Supported by the US National Institutes of Health (R01 AI-05753 and R01 AI-074378 to A. Cerutti and S10RR09145), Catalan Institute for Research and Advanced Studies (A. Cerutti), Fundacio’ Institut Municipal d’Investigació Mèdica (A. Cerutti), Ministerio de Ciencia e Innovación (SAF 2008-02725 to A. Cerutti), The Irma T. Hirschl Charitable Trust (A. Cerutti), Comissionat per a Universitats i Recerca del Departament d’Innovació, Universitats i Empresa de la Generalitat de Catalunya (R.S.), Programa Juán de la Cierva (I.P.), Fondazione C. Golgi and Centro Immunodeficienze Mario di Martino (A. Plebani), TÁMOP (4.2.2-08/1-2008-0015 to L.M.), the US National Institutes of Health–National Cancer Institute (5R24 CA095823) and the National Science Foundation (DBI-9724504).
PY - 2010/9
Y1 - 2010/9
N2 - BAFF and APRIL are innate immune mediators that trigger immunoglobulin G (IgG) and IgA class-switch recombination (CSR) in B cells by engaging the receptor TACI. The mechanism that underlies CSR signaling by TACI remains unknown. Here we found that the cytoplasmic domain of TACI encompasses a conserved motif that bound MyD88, an adaptor that activates transcription factor NF-κB signaling pathways via a Toll-interleukin 1 (IL-1) receptor (TIR) domain. TACI lacks a TIR domain, yet triggered CSR via the DNA-editing enzyme AID by activating NF-κB through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway. TACI-induced CSR was impaired in mice and humans lacking MyD88 or the kinase IRAK4, which indicates that MyD88 controls a B cell-intrinsic, TIR-independent, TACI-dependent pathway for immunoglobulin diversification.
AB - BAFF and APRIL are innate immune mediators that trigger immunoglobulin G (IgG) and IgA class-switch recombination (CSR) in B cells by engaging the receptor TACI. The mechanism that underlies CSR signaling by TACI remains unknown. Here we found that the cytoplasmic domain of TACI encompasses a conserved motif that bound MyD88, an adaptor that activates transcription factor NF-κB signaling pathways via a Toll-interleukin 1 (IL-1) receptor (TIR) domain. TACI lacks a TIR domain, yet triggered CSR via the DNA-editing enzyme AID by activating NF-κB through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway. TACI-induced CSR was impaired in mice and humans lacking MyD88 or the kinase IRAK4, which indicates that MyD88 controls a B cell-intrinsic, TIR-independent, TACI-dependent pathway for immunoglobulin diversification.
UR - https://www.scopus.com/pages/publications/77955921430
U2 - 10.1038/ni.1914
DO - 10.1038/ni.1914
M3 - Article
C2 - 20676093
AN - SCOPUS:77955921430
SN - 1529-2908
VL - 11
SP - 836
EP - 845
JO - Nature Immunology
JF - Nature Immunology
IS - 9
ER -