Immunological characterization of C3H mice congenic for Fas lprcg,C3H/HeJ- Fas lprcg / Fas lprcg

Abstract

Fas^lpr (lpr) and Fas^lprcg (lpr^cg ) are allelic mutations of the Fas gene that is involved in apoptosis or programmed cell death. Lpr greatly reduces the expression of functional Fas and lpr^cg expresses the death domain-disabled, non-functional Fas on the cell surface. C3H/HeJ mice congenic for lpr^cg (C3H-lpr^cg ) were established and compared with C3H/HeJ-lpr/lpr (C3H-lpr) mice for their immunological and pathological features. Lymphadenopathy, splenomegaly, development of CD4^-CD8^-B220⁺ or double-negative (DN) T cells, renal pathology, and lymphoid cell infiltration in the lung and liver were not significantly different between C3H-lpr^cg and C3H-lpr mice. Noticeably, however, the production of serum immunoglobulin, autoantibodies against double-strand DNA and serum immune complexes were significantly lower in C3H-lpr^cg than in C3H-lpr mice. The results indicate that the death signal through the death domain of Fas is responsible for lymphoproliferation due to the accumulation of DN T cells and suggest that the region of Fas outside the death domain may be involved in autoantibody production. The newly-developed congenic C3H-lpr^cg mice will provide a powerful tool for research into the function of Fas apart from apoptosis.