Search

The frequency and nature of IgG anti-cardiolipin and anti-ds-DNA antibodies among MRL/lpr, MRL/+ and NZB/W Fl mice (murine lupus strains) and non-autoimmune inbred strains of mice (NIH/Swiss and Balb/c) were analysed by ELISA. High titres of anti-ds-DNA were detected in autoimmune strains (MRL/lpr, 69%; MRL/+, 50%; and NZB/W, 80% positive), whereas anti-cardiolipin antibodies were detected only in MRL/lpr (69%) and MRL/+ (17%) mice. IgG subclass analysis of these antibodies in 20 MRL/lpr sera revealed that all four subclasses were represented. When tested for fine antigenic specificity, anti-cardiolipin antibodies in MRL/lpr and MRL/+ mice bound to acidic phospholipids rather than to neutral phospholipids and were not inhibited by DNA. In MRL/lpr mice, anti-cardiolipin antibodies were first detected at 2 months, peaked around 5 months and then declined preterminally. To determine whether complications associated with anti-cardiolipin antibodies were present in MRL/lpr mice, blood counts were performed and litter sizes were determined. Although no significant decreases in the red and white blood cell counts were observed in MRL/lpr mice, platelet counts were significantly lower compared with NIH/Swiss (P<0.001) and Balb/c (P<0.005) mice. MRL/lpr mice had significantly fewer pups per delivery compared with a normal strain (MRL/lpr, 5.3 + 2.6; NIH/Swiss, 7.2 ± 2.1; P<0.002). These observations indicate that the serological characteristics of IgG anti-cardiolipin antibodies in MRL/ lpr mice are similar to those of anti-cardiolipin antibodies in humans with lupus. Whether these autoantibodies are pathogenetically related to thrombocytopenia and a small litter size in MRL/lpr mice remains to be determined. [ABSTRACT FROM AUTHOR]

NZB mice were found to produce natural thymocytotoxic autoantibody in high prevalence and antibody titre. This autoantibody in NZB mice was detectable by the cytotoxicity test at both 4°C and 37°C; the prevalence and antibody titre were generally higher at 4°C. Mice of other strains also produced natural thymocytotoxic autoantibody although in lower prevalence and antibody titre and in some instances the activity was greater at 37°C than at 4°C. Natural thymocytotoxic autoantibody in NZB mice reacted equally with the thymocytes of virtually all strains of mice tested but to a lesser degree with the thymocytes of SJL/J mice. A serum pool obtained from old NZB mice had an extremely high titre of natural thymocytotoxic autoantibody (l:1024 at 4°C). Nevertheless, the cells in lymph nodes, spleen and blood leucocytes were only partially sensitive to this serum pool, and bone marrow cells were for the most part negative. By absorption, the antigen reacting with natural thymocytotoxic autoantibody was found in thymus, lymph node, spleen and brain of adult mice, thymus of newborn mice and some leukaemias. Natural thymocytotoxic autoantibody in NZB mice was an IgMglobulin as determined by sensitivity to 2-mercaptoethanol treatment and by Sephadex G-200 column chromatography in contrast to other natural antibodies (antinuclear, antierythrocyte and G antibodies) of IgG-globulin class. NZB mice also produced natural antibodies against thymocytes of the rat and the hamster; these antibodies were species-specific and did not react with the thymocytes of any but the homologous species. [ABSTRACT FROM AUTHOR]

Changes in subpopulations of lymphoid cells of normal (CBA) and autoimmune (NZB) mice were studied as a function of age, by observing migration patterns of 51Cr labelled lymph node, spleen and thymus cells from donors aged 8 days to 12 months. The method permits analysis of the proportions and numbers of recirculating and non-recirculating lymphocytes in lymphoid compartments. Changes in the lymphoid populations of CBA mice were found, which could be attributed to the normal processes of maturation and senescence. In NZB mice relative and absolute decreases in the recirculating cell content of lymph node and spleen were observed which coincided with the time of development of autoimmunity. The significance of these results, in relation to altered immunocompetence with age, is discussed. [ABSTRACT FROM AUTHOR]

Polyanion-immunoglobulin complexes, considered important factors in the pathogenesis of glomerulonephritis common in systemic lupus erythematosus, were found and isolated from sera of NZB mice by selectively binding them to an anion-exchange cellulose (DE52). Accurate quantification of such complexes was possible, in terms of immunoglobulin content, by means of an antiglobulin complement-fixation assay. In sera of NZB mice the concentration of immune complexes increased up to about 11 months of age and then it declined, whereas in the sera of the C57B1 and HaICR strains of mice, which do not develop spontaneous glomerulonephritis, the concentration was lower initially but increased steadily with increasing age and reached an equivalent level at about 27 months. The complexes were composed primarily of immunoglobulins of the IgG class bound to native DNA. The finding of significant levels of circulating immune complexes in mouse strains without renal disease suggests that such complexes, although necessary, might not be sufficient and solely responsible for overt glomerulonephritis. [ABSTRACT FROM AUTHOR]

NZB mice naturally produce an autoantibody which in the presence of complement is specifically cytotoxic for thymocytes and thymus-dependent lymphocytes (T-cells) in the peripheral lymphoid tissues (lymph nodes and spleen) and the circulation of mice. Using a direct cytotoxicity test with a NZB mouse serum pool which contained the high titred autoantibody, a progressive decrease was observed with a g e in the proportion of the autoantibody-sensitive cells in mesenteric lymph node, spleen, and blood of NZB mice in comparison with mice of other strains (C57BL/ 6J and NZW). The numerical decrease in the population of autoantibody-sensitive cells was evident at younger age and greater degree in the peripheral blood than in t h e lymph node and spleen. The age-decrease in the number of autoantibody sensitive cells in lymph node and spleen contrasted with the numerical increase in nucleated cells in these organs. The age-decrease in the proportion and number of t h e autoantibody-sensitive cells in the blood exceeded the decrease in the blood lymphocyte count. This finding indicated that T-cells in the blood are selectively depleted with the ageing of NZB mice. A similar observation was made on the blood lymphocytes of (NZB × NZW)F1 hybrid mice. The depletion of T-cells in the blood in association with the production of natural thymocytotoxic autoantibody is termed autoimmune thymus-dependent lymphocytopenia. [ABSTRACT FROM AUTHOR]