The Myeloma Risk Variant of TNFRSF13B Shows Reduced NF-κB Signalling Activity in HEK293 Cells

Area of Science:

• Immunology
• Genetics

Background:

• TNFRSF13B gene encodes TACI (transmembrane activator and CAML interactor).
• A single nucleotide variant, rs34562254, in TNFRSF13B is associated with increased risk of myeloma and MGUS.
• This variant results in a proline to leucine substitution (P251L/P205L) in TACI isoforms.

Purpose of the Study:

• To investigate the functional impact of the TACI P205L variant on NF-κB signaling.
• To explore the potential indirect mechanism linking TACI P205L to myeloma risk.

Main Methods:

• Utilized HEK293 cells for experiments.
• Employed an NF-κB-luciferase reporter assay to measure NF-κB signaling.
• Quantified NF-κB p65 subcellular localization.

Main Results:

• The TACI P205L variant exhibited significantly reduced NF-κB activity compared to the wild-type short isoform.
• NF-κB p65 subcellular localization patterns were altered in the presence of the variant.

Conclusions:

• The TACI P205L variant demonstrates impaired NF-κB signaling.
• This impairment suggests an indirect contribution of the TACI P205L variant to the elevated risk of myeloma.