The use of congenital immunologic mutants to probe autoimmune disease in New Zealand mice.
To further our understanding of autoimmunity, many laboratories have concentrated on the study and manipulation of murine lupus in several strains. Although direct extrapolation of data from animal to man must proceed with caution, the use of such animal systems, both in vitro and in vivo, has been an enormous help in the development of immunologic concepts. Our laboratory has been studying murine lupus by selective breeding of specific genetic immune defects onto New Zealand mice. Specifically, we have used congenital immunologic mutations resulting in asplenia (Dh/+), athymia (nu/nu) and immunodeficiency (Xid) as a means of probing the natural history of immunopathology in one such murine model of autoimmunity New Zealand (NZ) mice. These studies have provided important insights into the ontogeny of autoimmunity. NZB.Xid mice have been particularly valuable and have become a useful tool for dissecting the B cell defects of NZ mice. The Xid gene is dominant over the premature polyclonal activation of NZB mice and acts almost exclusively on B cells that are involved in autoantibody production in NZB mice. Nonetheless, the fact that autoantibody production can occur in a small percent of very old NZB.Xid mice, which have the same phenotype as other NZB.Xid mice, suggests that it can be produced by a mechanism other than a generalized polyclonal expansion and is not dependent on the circulatory or splenic frequency of the Lyb 5 subset of cells. Finally, NZB.Xid mice are unable to produce autoantibodies even after maturing in an aged NZB microenvironment, which suggests that the cell population missing in NZB.Xid mice are important for autoantibody production.
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D051379:Mice; D008814:Mice, Inbred NZB / Q000276:immunology*; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology