Genotype-restricted lymphoproliferation in autoimmune lpr mice.

Transfer of bone marrow (BM) from autoimmunity-prone mice homozygous for the new lymphoproliferation mutation (lprcg) caused systemic lymphoproliferation in irradiated lprcg/lprcg recipients but not in irradiated +/+ recipient (J. Exp. Med. 1990. 171:519; Eur. J. Immunol. 1991.21: 63). It was thus hypothesized that the lprcg gene expresses its function at lymph nodes (LN) to provide anomalous lprcg/lprcg lymphoid cells with the environment where they can accumulate. This was confirmed by LN transplantation and BM transfer studies. In the LN transplantation study lprcg/lprcg LN grafts with or without in vitro irradiation swelled and lprcg/+ LN grafts were slightly hyperplastic or apparently normal; however, whereas +/+ LN grafts atrophied in lprcg/lprcg recipients, they were all histologically normal in +/+ and lprcg/+ recipients. Irradiation of lprcg/lprcg LN grafts significantly retarded their swelling in lprcg/lprcg recipients. In the BM transfer study lprcg/lprcg BM cells caused systemic lymphoproliferation in lpr/lpr and gld/+, lprcg/+ recipients and sporadic LN swelling in lprcg/+ recipients but LN atrophy in gld/gld recipients. In the study using both techniques in combination, lpr/lpr LN grafts swelled but gld/gld LN grafts atrophied in lprcg/lprcg BM----+/+ chimeras. All the swollen LN contained Thy-1+CD4-CD8 lymphoid cells or "double-negative (DN)" T cells characteristic of the lpr disease. Analysis of DNA restriction fragment length polymorphism demonstrated that lprcg/lprcg DN cells derived from lprcg/lprcg BM cells accumulated in lpr/lpr LN and gld/+, lprcg/+LN. The following conclusions have been drawn: (a) the lprcg gene determines the ability of lprcg/lprcg DN cell to accumulate in LN; (b) this genetic trait is not totally recessive differing from lymphoproliferation; (c) lpr/lpr LN and gld/+, lprcg/+ LN are equivalent to lprcg/lprcg LN in the receptivity of lprcg/lprcg DN cell accumulation thus supporting the allelism of lpr with lprcg and the complementation between gld and lprcg (J. Exp. Med. 1990. 171:519), respectively; (d) the ability of lprcg/lprcg LN to accumulate DN cells is partially resistant to irradiation; (e) lprcg/lprcg DN cells may cause atrophy of gld/gld LN and +/+ LN and (f) the gld and lpr genes are different from each other in the phenotype expressed at the LN site.