Lymphadenopathy induced by the cooperation between lprcg and gld genes is of lpr but not of gld phenotype

Mice homozygous for the lpr (lymphoproliferation), lpr^cg or gld (generalized lymphoproliferative disease) mutation develop strikingly similar lymphadenopathy with expansion of B220⁺ CD4^? CD8^? double-negative (DN) T cells and autoimmunity. To elucidate the roles of bone marrow (BM) and lymph node (LN) in lymphoproliferation, BM and LN were transplanted simultaneously into normal or +/+ mice in various genotype combinations. In lpr/lpr or lpr^cg/lpr^cg BM recipients grafted lpr/lpr and lpr^cg/lpr^cg LN swelled but +/+ and gld/gld LN atrophied. In gld/gld BM recipients all of LN swelled regardless of genotype. Thus, lpr and lpr^cg are phenotypically different from gld in the interaction of BM-derived DN T cells and +/+ LN. Compared with lpr the lpr^cg gene differs in its ability to complement with gld in induction of lymphadenopathy. To determine whether lymphoproliferation induced by the cooperation between lpr^cg and gld is of lpr or gld phenotype, LN of various genotypes were implanted into double heterozygous lpr^cg/+, gld/+ mice. Grafted lpr/lpr and lpr^cg/lpr^cg LN swelled but +/+ and gld/gld LN atrophied, indicating that it is of lpr phenotype. Moreover, grafted lpr^cg/+ LN swelled but lpr/+ LN atrophied, indicating that, in the heterozygous state, lpr^cg is phenotypically different from lpr as it allows for LN accumulation of DN T cells induced by lpr^cg-gld cooperation.