IgG autoantibody activity in normal mouse serum is controlled by IgM.
In the serum of normal BALB/c mice, IgG antibody reactivity to mouse actin and tubulin, DNA, and TNP groups was very low compared to that of the IgM. This activity was considerably increased when IgG was separated, by affinity chromatography on protein A-Sepharose, whereas no difference in the IgM activity was observed. Addition of IgM to IgG isolated from the same serum resulted in the inhibition of IgG binding to these Ag. Isolation of IgG antibodies on actin, TNP, and tubulin immunoadsorbents has indicated that at least part of the IgG antibodies is polyreactive. In order to understand this inhibition better, experiments with F(ab')2 fragments of IgG were performed. IgM inhibited the binding of F(ab')2 to the antigens in a dose-dependent manner and reacted with immobilized F(ab')2. IgM isolated on F(ab')2 immunoadsorbent, as compared to the initial IgM preparation, were less active toward the Ag but more inhibitory for IgG binding to the Ag. In some pathologic situations, IgM failed to inhibit some IgG antibody activities. The anti-DNA IgG activity from (NZB x NZW)F1 mice was not affected by autologous IgM. Similarly the anti-tubulin IgG from mice infected with Trypanosoma cruzi were less inhibited by IgM from autologous serum than antitubulin IgG from normal mice. These results are compatible with the existence in normal mice of an idiotypic-like network, regulating via an IgM population in the serum, the binding of IgG autoantibodies to self Ag. Modifications of this idiotype-anti-idiotype system might lead to the expression and/or expansion of autoreactive IgG-producing clones.
Adib
M
M
Unité d'Immunocytochimie, CNRS URA 359, Institut Pasteur, Paris, France.
Ragimbeau
J
J
Avrameas
S
S
Ternynck
T
T
D000199:Actins / Q000276:immunology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis*; D004247:DNA / Q000276:immunology; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G / Q000032:analysis*; D007075:Immunoglobulin M / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014404:Tubulin / Q000276:immunology
D000199:Actins; D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014404:Tubulin; D004247:DNA