Functional analyses of lpr gene in MRL/Mp-lpr/lpr mice. Role of lymph node stromal cells in lpr-lymphadenopathy.
To clarify the mechanism by which the lpr gene causes lymphadenopathy, we established an experimental system to induce lymph node (LN) swelling in unaffected mice. In MRL-(+)/+ mice that had been 5 Gy-irradiated and grafted with bone marrow cells (BMCs) plus LN from MRL-lpr/lpr mice, a remarkable enlargement of the LN grafts was seen. The enlarged grafts lacked normal LN structure and were indistinguishable from LNs of MRL-lpr/lpr mice. The induction of LN swelling by this method was achieved not only in [MRL-lpr/lpr-->MRL-(+)/+] but also in [MRL-lpr/lpr-->BALB/c], [MRL-lpr/lpr-->C3H], [B6-lpr/lpr-->B10.Thy1.1], and [B6-lpr/lpr-->BALB/c] combinations. Furthermore, the lpr/lpr LN grafts developed lymph node swelling even without the transplantation of BMCs. Most cells in the grafted LNs disappeared within a few days, and large clear fibroblast-like cells then became dominant for 1 to 4 weeks. Thereafter, lymphoid cells increased and had filled the graft by the 8th week. The LN grafts obtained from MRL-lpr/lpr (but not MRL-(+)/+) mice showed the ability to transfer LN node swelling into the secondary MRL-(+)/+ hosts two weeks after the primary transplantation. These results strongly suggest that the fibroblast-like LN stromal cells play a crucial role in lpr-associated lymphadenopathy.
Ohnishi-Inoue
Y
Y
First Department of Pathology, Kansai Medical University, Osaka, Japan.
Yasumizu
R
R
Sugiura
K
K
Nagata
N
N
Fan
H
H
Oyaizu
N
N
Inaba
M
M
Toki
J
J
Ikehara
S
S
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D005347:Fibroblasts / Q000473:pathology; D005796:Genes; D005838:Genotype; D006984:Hypertrophy; D016219:Immunotherapy, Adoptive; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D008206:Lymphatic Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics / Q000276:immunology; D008815:Mice, Inbred Strains / Q000235:genetics* / Q000276:immunology; D008817:Mice, Mutant Strains / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D011828:Radiation Chimera