Lupus & antiphospholipid syndrome

Type I interferons enhance B cell activation and promote differentiation of double negative 2 cells in SLE

Lupus Sci MedPublished Mechanistic study

Authors' conclusion

Type I IFN promotes human B cell activation and DN2 differentiation, supporting IFN blockade as a strategy to reduce pathogenic B cells and prevent SLE flares.

Study context

Population
Patients with SLE (quiescent or recently flaring) and healthy controls; PBMCs analysed
Participants
18 / 25 / 41
Comparison
Recently flaring vs quiescent SLE vs healthy controls; HC naïve B cells stimulated with and without interferon (IFNs)
  • Healthy controls (HCs)n = 18reference
  • Quiescentn = 25
  • Flaringn = 41
Methodological detailscytometry by time of flight, in vitro stimulation
  • Cytometry by time of flight
  • In vitro stimulation

Main finding

As reported in the abstract

  • All B cell subsets exhibited higher ISP levels in flaring than quiescent disease
  • DN2 cells more abundant in flaring patients and correlated with the ISP score
  • ISP scores strongly correlated with markers of B cell activation, even after controlling for disease status
  • In vitro, IFNα and IFNβ promoted DN2 differentiation in HC B cells
  • In patients treated with anifrolumab, DN2 frequency and ISP scores significantly decreased

Original publication

Type I interferons enhance B cell activation and promote differentiation of double negative 2 cells in SLE. Lupus Sci Med. Published 28 June 2026. doi:10.1136/lupus-2026-002042

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