Lymphoid cell accumulation in salivary glands of autoimmune MRL mice can be due to impaired apoptosis

Abstract

MRL-lpr mice and the congenic strain MRL +/+ exhibit pathological abnormalities in the salivary glands similar to Sjögren's syndrome in humans. The lpr genotype has been identified as a mutation in the gene encoding Fas which is a cell surface protein that mediates apoptosis. The mutation is leaky, allowing for low levels of the APO-1/Fas (CD95) receptor and partial activity of Fas/Fas ligand-mediated programmed cell death in this strain. To examine the expression of Fas in situ, the authors 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 apoptotic cells the authors used the terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling (TUNEL) method. Thymus 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 similar expression of Fas in lymph nodes as lpr mice. The Fas protein was detected among infiltrating mononuclear cells in the salivary glands of both lpr and +/+ mice. Apoptotic cells were found in the thymus with similar frequency in all three strains, while in the lymph nodes only BALB/c mice showed apoptosis. There was no, or very low, frequency of apoptosis among infiltrating mononuclear cells in salivary glands of both 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 mice. Based on analysis of apoptotic activity, the impaired Fas in autoimmune MRL mice seems to affect primarily the peripheral organs.