The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88

Bing He, Raul Santamaria, Weifeng Xu, Montserrat Cols, Kang Chen, Irene Puga, Meimei Shan, Huabao Xiong, James B. Bussel, April Chiu, Anne Puel, Jeanine Reichenbach, L. Máródi, Rainer Döffinger, Julia Vasconcelos, Andrew Issekutz, Jens Krause, Graham Davies, Xiaoxia Li, Bodo Grimbacher & 6 others Alessandro Plebani, Eric Meffre, Capucine Picard, Charlotte Cunningham-Rundles, Jean Laurent Casanova, Andrea Cerutti

Research output: Contribution to journalArticle

214 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)836-845
Number of pages10
JournalNature Immunology
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 2010

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Immunoglobulin Class Switching
Genetic Recombination
B-Lymphocytes
Transmembrane Activator and CAML Interactor Protein
TNF Receptor-Associated Factor 6
Interleukin-1 Receptors
Toll-Like Receptors
Immunoglobulin A
Immunoglobulins
Transcription Factors
Phosphotransferases
Immunoglobulin G
DNA
Enzymes

ASJC Scopus subject areas

  • Immunology

Cite this

The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. / He, Bing; Santamaria, Raul; Xu, Weifeng; Cols, Montserrat; Chen, Kang; Puga, Irene; Shan, Meimei; Xiong, Huabao; Bussel, James B.; Chiu, April; Puel, Anne; Reichenbach, Jeanine; Máródi, L.; Döffinger, Rainer; Vasconcelos, Julia; Issekutz, Andrew; Krause, Jens; Davies, Graham; Li, Xiaoxia; Grimbacher, Bodo; Plebani, Alessandro; Meffre, Eric; Picard, Capucine; Cunningham-Rundles, Charlotte; Casanova, Jean Laurent; Cerutti, Andrea.

In: Nature Immunology, Vol. 11, No. 9, 09.2010, p. 836-845.

Research output: Contribution to journalArticle

He, B, Santamaria, R, Xu, W, Cols, M, Chen, K, Puga, I, Shan, M, Xiong, H, Bussel, JB, Chiu, A, Puel, A, Reichenbach, J, Máródi, L, Döffinger, R, Vasconcelos, J, Issekutz, A, Krause, J, Davies, G, Li, X, Grimbacher, B, Plebani, A, Meffre, E, Picard, C, Cunningham-Rundles, C, Casanova, JL & Cerutti, A 2010, 'The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88', Nature Immunology, vol. 11, no. 9, pp. 836-845. https://doi.org/10.1038/ni.1914
He, Bing ; Santamaria, Raul ; Xu, Weifeng ; Cols, Montserrat ; Chen, Kang ; Puga, Irene ; Shan, Meimei ; Xiong, Huabao ; Bussel, James B. ; Chiu, April ; Puel, Anne ; Reichenbach, Jeanine ; Máródi, L. ; Döffinger, Rainer ; Vasconcelos, Julia ; Issekutz, Andrew ; Krause, Jens ; Davies, Graham ; Li, Xiaoxia ; Grimbacher, Bodo ; Plebani, Alessandro ; Meffre, Eric ; Picard, Capucine ; Cunningham-Rundles, Charlotte ; Casanova, Jean Laurent ; Cerutti, Andrea. / The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. In: Nature Immunology. 2010 ; Vol. 11, No. 9. pp. 836-845.
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