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Nat Immunol. 2010 Sep;11(9):836-45. doi: 10.1038/ni.1914. Epub 2010 Aug 1.

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

Author information

1
Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.

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.

PMID:
20676093
PMCID:
PMC3047500
DOI:
10.1038/ni.1914
[Indexed for MEDLINE]
Free PMC Article

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