Autoantibody to liver-specific lipoprotein in the mouse: regulation by naturally occurring autoantigen specific...

Indirect and direct evidence is presented that normal, non-immune mice have cells which suppress antibody production to murine liver specific lipoprotein (LSP) autoantigens with little or no effect on the response to a closely related foreign antigen complex, rabbit LSP. Suppressor control mechanisms were suggested in low responder BALB/c mice which produced LSP autoantibody only after exposure to low dose X-irradiation or treatment with cyclophosphamide. Adoptive transfer experiments in X-irradiated BALB/c mice and untreated C57BL/6 mice showed that cells from normal mouse spleen prevented LSP autoantibody production when put into the circulation of mice prior to immunization with foreign rabbit LSP. This suppressor activity was destroyed by treatment with antisera to T cells and by low dose X-irradiation. The normal spleen cells were ineffective as suppressors if given after primary immunization with rabbit LSP had commenced. It is suggested that the adoptive transfer of normal spleen cells prior to immunization with foreign LSP supplements homeostatic mechanisms in favour of tolerance to LSP autoantigen. It is argued that the LSP autoantibody response in the mouse is a unique model for the study of autoantigen specific naturally occurring suppression.