Induction of natural autoantibody activity following treatment of human immunoglobulin with dissociating agents.
Treatment of normal polyclonal human IgG and of F(ab')2 fragments of IgG with 6.0 M urea, 1.3 M sodium thiocyanate or with acidic buffers (pH 2.0), resulted in a dramatic and selective enhancement of the preexisting antibody reactivity with self antigens. Enhanced antibody activity revealed by the dissociating agents was inhibited by the addition of an excess of the relevant soluble antigen. Human monoclonal IgG, including four different IgG1m(1) V(H)3+ and V(K)3+ paraproteins differing only in their CDRs, exhibited different changes in reactivity following urea treatment indicating major involvement of CDR sequences. The calculated dissociation constant of the binding reaction of normal IgG to the self antigen actin was 10(-6) M, whether IgG had been treated or not, indicating that the treatment increased the proportion of available self-reactive molecules instead of increasing the affinity of the preexisting natural autoantibodies. Enhanced autoreactivity was not due to aggregation of Ig, unmasking of the antibody site by removal of low MW antigens, nor to the denaturation of natural Id-anti-Id complexes. Taken together, these results suggest that treatment of Ig with dissociating agent results in the exposure of basic polyreactive antibody structures. The enhancement of reactivity may be of relevance in physiology of mucosal immunity and in therapeutic immunomodulation.
Bouvet
J P
JP
Unité d'Immunopathologie Humaine, INSERM U430, Université Pierre et Marie-Curie, Paris, Paris VI, France. jean-pierre.bouvet@brs.ap-hop-paris.fr
Stahl
D
D
Rose
S
S
Quan
C P
CP
Kazatchkine
M D
MD
Kaveri
S V
SV
D000199:Actins / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D002021:Buffers; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000627:therapeutic use; D013861:Thiocyanates; D014508:Urea
D000199:Actins; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D002021:Buffers; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D013861:Thiocyanates; C024553:sodium thiocyanate; D014508:Urea