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), lprcg 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 lprcg/lprcg BM recipients grafted lpr/lpr and lprcg/lprcg LN swelled but +/+ and gld/gld LN atrophied. In gld/gld BM recipients all of LN swelled regardless of genotype. Thus, lpr and lprcg are phenotypically different from gld in the interaction of BM-derived DN T cells and +/+ LN. Compared with lpr the lprcg gene differs in its ability to complement with gld in induction of lymphadenopathy. To determine whether lymphoproliferation induced by the cooperation between lprcg and gld is of lpr or gld phenotype, LN of various genotypes were implanted into double heterozygous lprcg/+, gld/+ mice. Grafted lpr/lpr and lprcg/lprcg LN swelled but +/+ and gld/gld LN atrophied, indicating that it is of lpr phenotype. Moreover, grafted lprcg/+ LN swelled but lpr/+ LN atrophied, indicating that, in the heterozygous state, lprcg is phenotypically different from lpr as it allows for LN accumulation of DN T cells induced by lprcg-gld cooperation.