Induction of circulating immune complexes and their renal localization after acute or chronic polyclonal B-cell activation in mice.
We investigated the ability of various polyclonal B-cell activators (PBA) to induce immunoglobulin synthesis, circulating immune complexes, and rheumatoid-factor-like autoantibodies. We found that, following the injection of a PBA--bacterial lipopolysaccharide, dextran sulfate, polyriboinosinic-polyribocytidilic acid, or purified protein derivative of tubercle bacteria--a transitory formation of circulating immune complexes occurred simultaneously with an increase in immunoglobulin production. The presence of circulating immune complexes after PBA administration was documented by the 125I-Clq-binding assay and the conglutinin-binding assay, and a partial characterization of this material was achieved. Although the kinetic properties, size, and composition of the immune complexes tested varied with the PBA used, the complexes detected in each group were inactivated by mild reduction and alkylation with 2-mercaptoethanol and were unaffected by DNase treatment. In the mice injected with bacterial lipopolysaccharide, the induction of circulating immune complexes correlated significantly with the presence of rheumatoid-factor-like antibodies, suggesting that this autoantibody may be present within the detected immune complexes. In tissues, glomerular deposits of IgM, IgG, and C3 were observed in a pattern compatible with the deposition of immune complexes. These deposits were progressively associated with marked glomerular abnormalities in mice chronically injected with LPS during 1 year. These data suggest that the induction of polyclonal antibody synthesis, which occurs in a variety of infectious or autoimmune diseases, may be responsible for the high incidence and persistence of immune complexes in these diseases. Such complexes would involve primarily autoantigens and corresponding autoantibodies, such as rheumatoid factor IgG complexes, without the participation of any specific bacterial, viral, or parasitic antigen.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology; D005260:Female; D007136:Immunoglobulins / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012217:Rheumatoid Factor / Q000032:analysis
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007136:Immunoglobulins; D007375:Interleukin-1; D004247:DNA; D012217:Rheumatoid Factor