The contribution of H-2bm12 and non H-2 background genes on murine lupus in NZB.H-2bm12/b mice.
We have previously demonstrated the influence of the I-Abm12 gene mutation on the appearance of IgG anti-dsDNA antibodies when placed on an NZB genetic background. To further enhance our understanding of the interaction of the bm12 mutation on disease expression, lethally irradiated NZB.H-2bm12/b F1 mice were reconstituted with T-cell-depleted bone marrow cells from 3- to 6-week-old donors of four different congenic strains, NZB.H-2bm12, NZB.H-2b, B6.C-H-2bm12 and C57BL/6 (H-2b) mice. All animals when then serially followed for the appearance of IgM and IgG anti-ss and dsDNA antibodies. Significant alterations of T-cell subsets, high levels of IgG anti-dsDNA antibodies and proteinuria were found only in recipient NZB.H-2bm12/b F1 mice that were reconstituted with T-cell-depleted NZB.H-2bm12 bone marrow cells. Such activity was not found in F1 mice engrafted and fully reconstituted with NZB.H-2b, B6.C-H-2bm12 or C57BL/6 (H-2b) T-cell depleted bone marrow cells. Additionally, to evaluate the importance of the NZB background (non-H-2) genes, we transferred T-cell-depleted bone marrow cells from NZB.H-2bm12 mice into H-2 compatible B6.C-H-2bm12 mice and vice versa. Without NZB background genes, an increase in CD4- CD8- T cells, IgG anti-dsDNA, splenomegaly, and proteinuria were not observed. These data suggest that the H-2bm12 gene and the NZB background genes in bone marrow-derived cells are both necessary for the altered expression of T-cell subsets and anti-DNA production.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine, School of Medicine, University of California, Davis 95616.
Y
Y
Watanabe
S H
SH
Yoshida
A A
AA
Ansari
M E
ME
Gershwin
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D016026:Bone Marrow Transplantation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB / Q000235:genetics* / Q000276:immunology; D011507:Proteinuria / Q000276:immunology; D013163:Splenomegaly / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000974:Antibodies, Antinuclear; D006183:H-2 Antigens