Age-Associated B Cells Contribute to Autoimmune Conditions
Age-associated B cells are a distinct population of B cells that grows in number with age. Evidence suggests that these cells are meaningfully dysfunctional and contribute to immune aging, including an impaired immune response and the chronic inflammation characteristic of later life. As researchers note here, there is plenty of evidence for age-associated B cells to contribute to autoimmune conditions as well. Temporary clearance of B cells is possible and has been demonstrated in animal models. The B cell population regenerates rapidly afterwards, but lacking the age-associated B cells that were present beforehand. This approach to therapy should be developed for widespread use.
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 (SLE), rheumatoid arthritis (RA), 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.
we have PLX3397 to deplete microglia, do we have anything similar for B cells?
@erasmus: monoclonal antibodies for B cell surface features, so immunotherapy: https://doi.org/10.1182/blood-2010-09-307983 I am not sure whether a small molecule approach exists.