title: The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88.
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-kappaB 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-kappaB 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.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Raul
authors.initials: R
authors.lastname: Santamaria
authors.forename: Weifeng
authors.initials: W
authors.lastname: Xu
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cols
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Irene
authors.initials: I
authors.lastname: Puga
authors.forename: Meimei
authors.initials: M
authors.lastname: Shan
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.forename: April
authors.initials: A
authors.lastname: Chiu
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Jeanine
authors.initials: J
authors.lastname: Reichenbach
authors.forename: László
authors.initials: L
authors.lastname: Marodi
authors.forename: Rainer
authors.initials: R
authors.lastname: Döffinger
authors.forename: Julia
authors.initials: J
authors.lastname: Vasconcelos
authors.forename: Andrew
authors.initials: A
authors.lastname: Issekutz
authors.forename: Jens
authors.initials: J
authors.lastname: Krause
authors.forename: Graham
authors.initials: G
authors.lastname: Davies
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Eric
authors.initials: E
authors.lastname: Meffre
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cunningham-Rundles
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerutti
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D015398:Signal Transduction; D053303:Transmembrane Activator and CAML Interactor Protein / Q000276:immunology*
chemical_list: D053594:Myeloid Differentiation Factor 88; D053303:Transmembrane Activator and CAML Interactor Protein