IGG INTERNALIZATION IN SENSORY NEURONS DEPENDS ON NEURONAL MATURITY AND DRG CELLULAR ENVIRONMENT

Autoantibodies have been implicated in neurological disorders and may contribute to the pathophysiology of sensory neuronopathy affecting dorsal root ganglia (DRG). Autoantibodies against intracellular epitopes of FGFR3 and Argonaute (AGO) proteins have been identified in a subset of patients. Their pathogenic role may depend on the ability of IgG to access intracellular targets. Here, we investigated whether human serum IgG can be internalized by DRG sensory neurons and the mechanisms underlying this process.
Four different models were used: DRG explants and purified sensory neurons derived from adult mice and mouse embryos. This experimental system allowed us to assess whether IgG internalization depends on neuronal maturity, the DRG environment, or both. Internalization was evaluated by exposing each model to human IgG and quantified using immunohistochemistry (IHC). To characterize the mechanism of internalization, Fc-receptors (FcR) expression was analyzed by IHC, and FcR–mediated endocytosis inhibitors were used.
IgG internalization did not occur in embryonic DRG neurons but was observed in ~47% of neurons in adult DRG explants and ~30% of purified sensory neurons. FcγR-I was expressed in DRG neurons from both adult and embryonic mice, whereas FcγR-II/III was detected only in non-neuronal cells of adult DRG. The neonatal FcR was strongly expressed in embryonic sensory neurons. Analyses of FcγR–mediated endocytosis inhibition are ongoing.
These results suggest that IgG internalization depends on neuronal maturity and requires interactions with surrounding cells, potentially linked to FcγR II/III expression. Ongoing studies of FcγR-mediated endocytosis will further elucidate the underlying mechanisms.