Bone marrow cell transfer of autoimmune diseases in a MRL strain of mice with a deficit in functional Fas ligand: Dissociation of arteritis from glomerulonephritis


Mitsuko R. Ito, MD, PhD, Department of Pathology, Ehime University School of Medicine, Sitsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. Email:


MRL/MpTn-gld/gld (MRL/gld) mice, which are deficient in a functional Fas ligand (FasL), spontaneously develop autoimmune diseases involving both lethal glomerulonephritis and systemic arteritis, while MRL/Mp-+/+ (MRL/+) and C3H/HeJ-gld/gld (C3H/gld) do not. To determine the cells responsible for the development of glomerulonephritis and arteritis, we transferred bone marrow cells from MRL/gld mice to undiseased MHC-compatible gld/gld or +/+ mice. In bone marrow irradiation chimeras, MRL/gld bone marrow cells were transferred to lethally irradiated MRL/+ or C3H/HeJ-+/+ (C3H/+) mice, and both recipients developed glomerulonephritis associated with hypergammaglobulinemia without causing graft-versus-host (GVH)-like diseases. However, a striking difference between them was that MRL/+ recipients developed arteritis, but C3H/+ recipients did not. In bone marrow mixed chimeras formed by transferring MRL/gld bone marrow cells to unirradiated mice, the MRL/gld bone marrow cells induced glomerulonephritis in C3H/gld mice, but not in C3H/+ and MRL/+ mice. These results indicate that bone marrow cells from MRL/gld mice can cause glomerulonephritis in mice, even in those with a C3H background, possibly if they survive longer by escaping from Fas-mediated apoptosis, while the development of arteritis requires the MRL genetic background in the re-cipients. This is the first report of the transfer of arteritis in lupus mice to undiseased recipients.