Age-Associated B Cells in Autoimmune Diseases: Pathogenesis and Clinical Implications

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Abstract
As a heterogeneous B cell subset, age-associated B cells (ABCs) exhibit distinct transcription profiles, extrafollicular differentiation processes, and multiple functions in autoimmunity. TLR7 and TLR9 signals, along with IFN-γ and IL-21 stimulation, are both essential for ABC differentiation, which is also regulated by chemokine receptors including CXCR3 and CCR2 and integrins including CD11b and CD11c. Given their functions in antigen uptake and presentation, autoantibody and proinflammatory cytokine secretion, and T helper cell activation, ABCs display potential in the prognosis, diagnosis, and therapy for autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, multiple sclerosis, neuromyelitis optica spectrum disorders, and ankylosing spondylitis. Specifically targeting ABCs by inhibiting T-bet and CD11c and activating CD11b and ARA2 represents potential therapeutic strategies for SLE and RA. Although single-cell sequencing technologies have recently revealed the heterogeneous characteristics of ABCs, further investigations to explore and validate ABC-target therapies are still warranted.
Funding Information
  • The National Natural Science Foundation of China (82473530, 82173425)
  • the Natural Science Foundation of Hunan Province of China (2024JJ4077)
  • the health research project of Hunan Provincial Health Commission of China (W20243055)
  • Hunan Outstanding Young Investigator (2020JJ2055)
  • The National Key R&D Program of China (2021YFC2702004)
  • the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-059)
  • The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2020-RC320-003)

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