The pathogenesis of autoimmunity in New Zealand mice.
In the past few years there has been an explosion of information in the area of NZ mouse research. This has reflected a general increase in knowledge and technology in cellular immunology and lymphocyte biology. Continuing research in many specific areas promises to expand this increasing data base. The numerous abnormalities of CMI in NZ mice chronicled in the past are currently being analyzed in terms of cell synergism rather than as simple effector mechanisms. Such analysis is indicating more selective rather than general impairment of CMI in aging NZ mice. Similarly, the allogeneic H-2 identical cytotoxic activity expressed by NZ mice and its relevance to autoimmune disease are being explored. In the area of suppressor functions in NZ mice, continued refinement and standardization of suppressor assays must be achieved before adequate interpretation of the present information can be made. Suppressor activity in aging NZ mice has been described as depressed, normal, and elevated. This is an area of acute interest. While the primary etiologic significance of T cell regulatory defects is currently being minimized, their possible secondary role in pathogenesis of autoimmune disease in NZ mice is being investigated. The recent discovery of a significant B cell abnormality present from birth in all SLE-prone murine strains has increased the probability that intrinsic B cell hyperactivity is a primary etiologic factor in murine autoimmunity. The hypersecretion of IgM and the increased incidence of B cell colony-forming units observed in NZ mice is being subjected to further genetic analysis in many laboratories. Similarly, the continued evaluation of the (CBA/N x NZB) hybrid promises to be enlightening, particularly the development of congeneic mice with the CBZ/N X chromosome on the NZB background. In addition, the development of H-2 congeneic NZB strains and immunoglobulin allotype congeneic NZB strains are proceeding. These strains will provide information on the possible roles of MHC and VH regions in autoimmune pathogenesis. The NZB.ch congeneic strain has already proven to be of great value. The continued development and further characterization of congenitally immunologic mutant NZ mice has been and will continue to be useful in elucidating the mechanism of autoimmune development in these animals. While NZ mice express a variety of host-viral interactions, recent genetic analysis suggests that viral infection is not a primary etiologic agent in the autoimmune disease of NZ mice. A well-defined clinical entity and a range of abnormalities have been delineated in NZ mice. The present goal is to define the cellular basis of autoimmunity through continued immunologic and genetic analysis of this important animal model of human autoimmune disease.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008814:Mice, Inbred NZB / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000974:Antibodies, Antinuclear