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

Overview

MeSH Major

  • B-Lymphocytes
  • Immunoglobulin Class Switching
  • Myeloid Differentiation Factor 88
  • Transmembrane Activator and CAML Interactor Protein

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.

publication date

  • September 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3047500

Digital Object Identifier (DOI)

  • 10.1038/ni.1914

PubMed ID

  • 20676093

Additional Document Info

start page

  • 836

end page

  • 45

volume

  • 11

number

  • 9