LYMPHOID-CELL ACCUMULATION IN SALIVARY-GLANDS OF AUTOIMMUNE MRL MICE CAN BE DUE TO IMPAIRED APOPTOSIS

MRL-lpr mice and the congenic strain MRL +/+ exhibit pathological abno rmalities in the salivary glands similar to Sjogren's syndrome in huma ns. The lpr genotype has been identified as a mutation in the gene enc oding Fas which is a cell surface protein that mediates apoptosis. The mutation is leaky, allowing for low levels of the APO-1/Fas (CD95) re ceptor and partial activity of Fas/Fas Ligand-mediated programmed cell death in this strain. To examine the expression of Fas in situ, the a uthors analysed thymus, lymph node and salivary gland tissue from BALB /c, MRL +/+ and MRL-lpr mice by an immunohistochemical technique (ABC- immunoperoxidase) using an anti-Fas (Jo2) antibody. For detection of a poptotic cells the authors used the terminal deoxynucleotidyl-transfer ase-mediated dUTP-digoxigenin nick end labelling (TUNEL) method. Thymu s from MRL +/+ and normal BALB/c mice showed a higher frequency of Fas expression than was seen in the lpr mice, but the +/+ mice had simila r expression of Fas in lymph nodes as lpr mice. The Fas protein was de tected among infiltrating mononuclear cells in the salivary glands of both lpr and +/+ mice. Apoptotic cells were found in the thymus with s imilar frequency in all three strains, while in the lymph nodes only B ALB/c mice showed apoptosis. There was no, or very low, frequency of a poptosis among infiltrating mononuclear cells in salivary glands of bo th MRL strains. In conclusion, despite mutation of the Fas gene in the MRL-lpr strain, there was nevertheless an expression of the apoptosis -related Fas protein in lymphoid tissue and salivary glands of these m ice. Based on analysis of apoptotic activity, the impaired Fas in auto immune MRL. mice seems to affect primarily the peripheral organs.