The Contribution of H-2bm12 and Non H-2 Background Genes on Murine Lupus in NZB.H-2bm12/b Mice

Yasuyuki Watanabe, Steven H. Yoshida, Aftab A. Ansari, M. Eric Gershwin

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)153-164
Number of pages12
JournalJournal of Autoimmunity
Volume7
Issue number2
DOIs
StatePublished - Apr 1994

Fingerprint

Bone Marrow Cells
T-Lymphocytes
Genes
T-Lymphocyte Subsets
Proteinuria
Anti-Idiotypic Antibodies
Immunoglobulin G
Mutation
Splenomegaly
Antibodies
DNA
anti-IgG

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 journalArticle

Watanabe, Yasuyuki ; Yoshida, Steven H. ; Ansari, Aftab A. ; Gershwin, M. Eric. / The Contribution of H-2bm12 and Non H-2 Background Genes on Murine Lupus in NZB.H-2bm12/b Mice. In: Journal of Autoimmunity. 1994 ; Vol. 7, No. 2. pp. 153-164.
@article{f77af031e1a74c17a36476b381e11a7c,
title = "The Contribution of H-2bm12 and Non H-2 Background Genes on Murine Lupus in NZB.H-2bm12/b Mice",
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.",
author = "Yasuyuki Watanabe and Yoshida, {Steven H.} and Ansari, {Aftab A.} and Gershwin, {M. Eric}",
year = "1994",
month = "4",
doi = "10.1006/jaut.1994.1012",
language = "English (US)",
volume = "7",
pages = "153--164",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
number = "2",

}

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 -