Introduction/Rationale: Neuropsychiatric lupus (NPSLE) encompasses a disease subset that impacts ~ 80% of patients with lupus. The Sle1,yaa lupus mouse model demonstrates anxiety and fatigue-like behaviors, and upregulate interferon-stimulated genes (ISG’s) in the brain as “patches”. Immunoglobulin deposits are also found in low levels at P10 throughout the neurovasculature before ISG’s increase. We investigate the autoantibody source which could drive IFN response in the brain.
Methods: To model chronic autoantibody load, Sle1,yaa serum was injected into the lateral ventricles of P1 B6 pups then retro-orbitally weekly. To provide a direct autoantibody source, antibody-secreting cells (ASC’s) from spleens, cervical lymph nodes, long bones, calvaria, and dura, of Sle1,yaa mice were injected into P1 B6 pups via the temporal vein.
Results: Mice receiving Sle1,yaa serum developed anxiety and showed immune complexes with elevated ISG’s near cerebral ventricles after 8 weeks. Mice receiving ASC’s from Sle1,yaa exhibited even stronger ISG expression after 4 weeks post-transfer. Using congenic markers, we observed that donor ASC’s migrated to the calvarium and dura; subsequently, IgG’s and C3 depositions were found alongside ISG patches in the brain. Further analysis of ASC composition showed increased plasmablasts (B220+CD138+) in the dura and long-lived plasma cells (B220-CD138+) in the calvarium.
Conclusion: We find that ASC’s from Sle1,yaa migrate to the CNS when engrafted at P1, driving IFN activity through immune complex depositions in the vasculature. This body of work provides insight into the mechanistic pathways of NPSLE.
