Abstract
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. These results also suggest that micro-environmental influences on the hematopoietic cells, including the thymic micro-environment, are necessary for the clinical appearance of murine lupus.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 153-164 |
| Number of pages | 12 |
| Journal | Journal of Autoimmunity |
| Volume | 7 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 1994 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
The Contribution of H-2bm12 and Non H-2 Background Genes on Murine Lupus in NZB.H-2bm12/b Mice. / Watanabe, Yasuyuki; Yoshida, Steven H.; Ansari, Aftab A.; Gershwin, M. Eric.
In: Journal of Autoimmunity, Vol. 7, No. 2, 04.1994, p. 153-164.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Contribution of H-2bm12 and Non H-2 Background Genes on Murine Lupus in NZB.H-2bm12/b Mice
AU - Watanabe, Yasuyuki
AU - Yoshida, Steven H.
AU - Ansari, Aftab A.
AU - Gershwin, M. Eric
PY - 1994/4
Y1 - 1994/4
N2 - 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. These results also suggest that micro-environmental influences on the hematopoietic cells, including the thymic micro-environment, are necessary for the clinical appearance of murine lupus.
AB - 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. These results also suggest that micro-environmental influences on the hematopoietic cells, including the thymic micro-environment, are necessary for the clinical appearance of murine lupus.
UR - http://www.scopus.com/inward/record.url?scp=0028176388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028176388&partnerID=8YFLogxK
U2 - 10.1006/jaut.1994.1012
DO - 10.1006/jaut.1994.1012
M3 - Article
C2 - 8037836
AN - SCOPUS:0028176388
VL - 7
SP - 153
EP - 164
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
IS - 2
ER -