Autoregulation of autoantibody synthesis in mercuric chloride nephritis in the Brown Norway rat II. Presence of antigen‐augmentable plaque‐forming cells in the spleen is associated with humoral factors behaving as auto‐anti‐idiotypic antibodies

Abstract

Plaque-forming cell (PFC) assays were used to investigate in vitro the immunoregulatory mechanism operating in the self-limiting anti-glomerular basement membrane (GBM) autoantibody response of Brown Norway (BN) rats given HgCl₂. The peak splenic PFC response occurred at day 9; thereafter the response fell sharply and was rarely detected after day 12. In specificity studies, incorporation of soluble GBM in the PFC assays of animals at day 9 had two distinct effects. In some animals the PFC response was inhibited in a dose-dependent fashion; however, in others an augmented number of PFC was observed. Furthermore, addition of GBM to the PFC mixture from certain animals studied at day 12 (or after) revealed large numbers of GBM-specific PFC when originally no GBM-specific PFC had been observed in the standard PFC assay. Sera from such animals, with and without antigen-augmentable PFC, were incorporated in the PFC mixture containing cells taken from day 9 animals. Sera from animals with revealed plaques could inhibit the GBM-specific PFC response of day 9 animals, whereas sera from animals without revealed plaques could not. Thus sera, from BN rats whose own antibody levels were falling, could inhibit the GBM-specific plaque-forming capability of cells from animals at an earlier stage of the autoimmune response and showed the potential importance of humoral factors, putatively anti-idiotypic antibodies, in effecting autoregulation of autoantibody formation in this model.