The Yaa Mutation Induces the Development of Autoimmunity in Mice Heterozygous for the gld (Generalized Lymphadenopathy Disease) Mutation

Mice homozygous for either the generalized lymphoproliferative disease (gld) or the lymphoproliferation (lpr) nonallelic mutations develop similar syndromes combining systemic autoimmunity and lymphoproliferative disease. Though essentially recessive, the lpr and gld mutations may be expressed in the heterozygous state: [lpr/+] mice displayed a mild "lpr-like" autoimmunity, and the [lprcg/+ gld/+] mice developed a "gld-like" disorder, showing interactions of the gld gene product with the nonallelic lprcg product. The Y-chromosome-linked autoimmune accelerator (Yaa) mutation being an autoimmunity accelerator, its association with an heterozygous gld gene taught also bring a gld-like syndrome. The [gld/+ Yaa] mice were shown here to develop autoimmunity and splenomegaly like [gld/gld] mice, but without their typical lymphadenopathy. Furthermore, the [gld/+ Yaa] splenomegaly was not due to the expansion of the unusual Thyl+B220+ T-cell subset typical of the gld syndrome, but rather to a polyclonal expansion of the major lymphoid cell subsets. Thus, the syndrome shown by [gld/+ Yaa ] mice was not a gld-like syndrome. This suggests that the interactions of the gld gene product with the Yaa product and with the lprcg product must be different.