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

Abstract 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.