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Publication : The contribution of H-2bm12 and non H-2 background genes on murine lupus in NZB.H-2bm12/b mice.

First Author  Watanabe Y Year  1994
Journal  J Autoimmun Volume  7
Issue  2 Pages  153-64
PubMed ID  8037836 Mgi Jnum  J:17841
Mgi Id  MGI:65867 Doi  10.1006/jaut.1994.1012
Citation  Watanabe Y, et al. (1994) The contribution of H-2bm12 and non H-2 background genes on murine lupus in NZB.H-2bm12/b mice. J Autoimmun 7(2):153-64
abstractText  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)
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