Absence of MZMs causes a loss of tolerance after repeated exposure to apoptotic cells. Eight-week-old female B6 mice were injected with 167 μg of CLs or an equivalent amount of control liposomes once a week for a period of 5 months. Some groups received intravenously 2 times weekly injections of 107 apoptotic thymocytes as indicated. (A) Sera were collected once monthly for a period of 5 months and examined for anti-dsDNA IgG reactivity as described elsewhere. (B) Survival curves for mice treated as described in panel A; n = 10 mice/group; *P < .05 as determined by the unpaired Student t test. (C) Kidney pathology score. H&E-stained renal sections from the from the groups described in panel A were collected at 5 months and scored for pathologic alteration as described in “Pathology.” GN indicates glomerulonephritis; n = 10 mice for all groups except CL/apop in which organs from 5 mice were examined. (D) Histology and immune complex deposition. Periodic acid Schiff reagent and H&E images from the mice examined in panel C (Di,ii,iv,v). (Diii,vi) Representative frozen renal sections from the groups indicated were stained for the presence of mouse IgG as described in “Pathology.” All images are 20× magnification. These experiments were repeated twice with similar results.
