Neuronal Uptake of Paraneoplastic and Other IgGs is Mediated by the Fc Portion of the IgG Molecule and Involves Previously Uncharacterized Neuronal FcγRI Receptors: Implications for Antibody-Mediated Neuronal Injury

Objective To investigate the mechanisms by which neurons take up paraneoplastic and other antibodies. Background Our laboratory has previously demonstrated that can both normal IgGs autoantibodies such as anti-Yo anti-Hu bind to their intracellular target antigens produce neuronal death. In this study we investigated how antibody uptake occurs. Design/Methods We first compared of Fab fragments with IgG Fc or whole IgGs. determine whether expressed receptors capable binding portion molecule, paraformaldehyde-fixed mouse rat brains sections were probed antibodies for three major types receptors: FcγRI (CD64), FcγRII, (CD32) FcγRIII (CD16). Neuronal antineuronal was between wild type mice knockout lacking receptor. also could be blocked IgG. Results Neurons incorporated fragment but not fragment. Intact taken neurons, immunospecific excluded. throughout cerebrum, cerebellum, brainstem showed immunolabeling FcγRI, only rare FcγRII FcγRIII. Uptake death observed in cultures from extensive controls. Paraneoplastic inhibited Conclusions requires interaction molecule uncharacterized receptors. provides a mechanism through reactive proteins gain access cause injury neurological disease. The observation possible implications patient treatment.