title: Circulating autoantibodies recognize and bind dying neurons following injury to the brain.
abstract: While it is known that autoimmune cells can protect against cell damage following traumatic injury of the brain, the role of autoantibodies in brain injury is less clear. Here we present evidence in adult rats that following a cortical lesion of the brain, circulating IgG autoantibodies bind to dying neurons in the vicinity of the lesion. At intervals that ranged from 4 h to 7 days after making a unilateral lesion of visual cortex, we observed neurons near the lesion that were immunopositive for rat IgG. Many of these IgG-positive neurons were in advanced stages of degeneration. The magnitude of the immunostaining observed was directly proportional to the percent reactivity to rat IgG of the antibodies that were used. Preadsorption of the antibodies with rat serum eliminated the immunostaining. In addition, immunostaining for serum albumin in sections through the cortical lesion was negative, supporting the conclusion that the positive staining for IgG does not result from the passive diffusion of serum proteins into injured cells. Instead, the evidence presented here strongly suggests that naturally occurring IgG autoantibodies bind specifically to dying neurons in the injured brain. We propose that this autoantibody binding may participate in the phagocytosis and removal of injured neurons.
authors.affiliation: Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Thor D
authors.initials: TD
authors.lastname: Stein
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Fedynyshyn
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Kalil
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000502:physiology; D001930:Brain Injuries / Q000276:immunology / Q000473:pathology*; D005404:Fixatives / Q000737:chemistry; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010544:Peroxidases / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D005404:Fixatives; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D011961:Receptors, Fc; D010544:Peroxidases