Autoantibody production and cytokine profiles of MHC class I (β2- microglobulin) gene deleted New Zealand Black (NZB) mice

Shao Yuan Chen, Yuichi Takeoka, Larry Pike-Nobile, Aftab A. Ansari, Richard Boyd, M. Eric Gershwin

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We established a colony of MHC class I deleted (knockout) NZB mice, which lack the β2 microglobulin gene (NZB.β2m(-/-)), to characterize the contribution of MHC class I to the thymic microenvironment abnormalities, autoantibody production and lupus-like disease of NZB mice. Using an extensive panel of well characterized monoclonal antibodies defining thymic epithelial and other stromal elements, we demonstrated that deletion of MHC class I molecules does not change the thymic abnormalities, including the presence of a cortical epithelial cell free region, ectopic expression of medullary epithelial antigens, and the irregular shape of the medullary epithelial network of NZB mice. Moreover, the decreased staining of MTS 33+ cells, a marker of premature thymocyte maturation, was also seen in NZB.β2m(-/-). However, although NZB.β2m(-/-) mice had approximately the same levels of IgM and IgG anti-ss and dsDNA antibodies when compared to control NZB mice, there were significant alterations in the incidence and onset of anti-erythrocyte antibody levels. NZB.β2m(-/-) had a lower incidence and a delayed onset of anti-erythrocyte autoantibody production compared to that seen in NZB mice. We also compared constitutive and PHA-P- driven levels of IFN-γ, IL-4, IL-6, and IL-12 in cells from NZB, NZB.β2/(- /-), and control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-γ, and a marked increase in IL-6 and IL-12 in NZB and NZB.β2m(-/-) mice.

Original languageEnglish (US)
Pages (from-to)318-327
Number of pages10
JournalClinical Immunology and Immunopathology
Volume84
Issue number3
DOIs
StatePublished - Sep 1997

Fingerprint

New Zealand
Autoantibodies
Cytokines
Genes
Interleukin-12
Interleukin-6
Erythrocytes
Incidence
Thymocytes
Inbred C57BL Mouse
Mitogens
Interleukin-4
Anti-Idiotypic Antibodies
Epithelial Cells
Monoclonal Antibodies
Staining and Labeling
Antigens
Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pathology and Forensic Medicine

Cite this

Autoantibody production and cytokine profiles of MHC class I (β2- microglobulin) gene deleted New Zealand Black (NZB) mice. / Chen, Shao Yuan; Takeoka, Yuichi; Pike-Nobile, Larry; Ansari, Aftab A.; Boyd, Richard; Gershwin, M. Eric.

In: Clinical Immunology and Immunopathology, Vol. 84, No. 3, 09.1997, p. 318-327.

Research output: Contribution to journalArticle

Chen, Shao Yuan ; Takeoka, Yuichi ; Pike-Nobile, Larry ; Ansari, Aftab A. ; Boyd, Richard ; Gershwin, M. Eric. / Autoantibody production and cytokine profiles of MHC class I (β2- microglobulin) gene deleted New Zealand Black (NZB) mice. In: Clinical Immunology and Immunopathology. 1997 ; Vol. 84, No. 3. pp. 318-327.
@article{4edff57056d14b90b7ddf6783217cecd,
title = "Autoantibody production and cytokine profiles of MHC class I (β2- microglobulin) gene deleted New Zealand Black (NZB) mice",
abstract = "We established a colony of MHC class I deleted (knockout) NZB mice, which lack the β2 microglobulin gene (NZB.β2m(-/-)), to characterize the contribution of MHC class I to the thymic microenvironment abnormalities, autoantibody production and lupus-like disease of NZB mice. Using an extensive panel of well characterized monoclonal antibodies defining thymic epithelial and other stromal elements, we demonstrated that deletion of MHC class I molecules does not change the thymic abnormalities, including the presence of a cortical epithelial cell free region, ectopic expression of medullary epithelial antigens, and the irregular shape of the medullary epithelial network of NZB mice. Moreover, the decreased staining of MTS 33+ cells, a marker of premature thymocyte maturation, was also seen in NZB.β2m(-/-). However, although NZB.β2m(-/-) mice had approximately the same levels of IgM and IgG anti-ss and dsDNA antibodies when compared to control NZB mice, there were significant alterations in the incidence and onset of anti-erythrocyte antibody levels. NZB.β2m(-/-) had a lower incidence and a delayed onset of anti-erythrocyte autoantibody production compared to that seen in NZB mice. We also compared constitutive and PHA-P- driven levels of IFN-γ, IL-4, IL-6, and IL-12 in cells from NZB, NZB.β2/(- /-), and control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-γ, and a marked increase in IL-6 and IL-12 in NZB and NZB.β2m(-/-) mice.",
author = "Chen, {Shao Yuan} and Yuichi Takeoka and Larry Pike-Nobile and Ansari, {Aftab A.} and Richard Boyd and Gershwin, {M. Eric}",
year = "1997",
month = "9",
doi = "10.1006/clin.1997.4398",
language = "English (US)",
volume = "84",
pages = "318--327",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Autoantibody production and cytokine profiles of MHC class I (β2- microglobulin) gene deleted New Zealand Black (NZB) mice

AU - Chen, Shao Yuan

AU - Takeoka, Yuichi

AU - Pike-Nobile, Larry

AU - Ansari, Aftab A.

AU - Boyd, Richard

AU - Gershwin, M. Eric

PY - 1997/9

Y1 - 1997/9

N2 - We established a colony of MHC class I deleted (knockout) NZB mice, which lack the β2 microglobulin gene (NZB.β2m(-/-)), to characterize the contribution of MHC class I to the thymic microenvironment abnormalities, autoantibody production and lupus-like disease of NZB mice. Using an extensive panel of well characterized monoclonal antibodies defining thymic epithelial and other stromal elements, we demonstrated that deletion of MHC class I molecules does not change the thymic abnormalities, including the presence of a cortical epithelial cell free region, ectopic expression of medullary epithelial antigens, and the irregular shape of the medullary epithelial network of NZB mice. Moreover, the decreased staining of MTS 33+ cells, a marker of premature thymocyte maturation, was also seen in NZB.β2m(-/-). However, although NZB.β2m(-/-) mice had approximately the same levels of IgM and IgG anti-ss and dsDNA antibodies when compared to control NZB mice, there were significant alterations in the incidence and onset of anti-erythrocyte antibody levels. NZB.β2m(-/-) had a lower incidence and a delayed onset of anti-erythrocyte autoantibody production compared to that seen in NZB mice. We also compared constitutive and PHA-P- driven levels of IFN-γ, IL-4, IL-6, and IL-12 in cells from NZB, NZB.β2/(- /-), and control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-γ, and a marked increase in IL-6 and IL-12 in NZB and NZB.β2m(-/-) mice.

AB - We established a colony of MHC class I deleted (knockout) NZB mice, which lack the β2 microglobulin gene (NZB.β2m(-/-)), to characterize the contribution of MHC class I to the thymic microenvironment abnormalities, autoantibody production and lupus-like disease of NZB mice. Using an extensive panel of well characterized monoclonal antibodies defining thymic epithelial and other stromal elements, we demonstrated that deletion of MHC class I molecules does not change the thymic abnormalities, including the presence of a cortical epithelial cell free region, ectopic expression of medullary epithelial antigens, and the irregular shape of the medullary epithelial network of NZB mice. Moreover, the decreased staining of MTS 33+ cells, a marker of premature thymocyte maturation, was also seen in NZB.β2m(-/-). However, although NZB.β2m(-/-) mice had approximately the same levels of IgM and IgG anti-ss and dsDNA antibodies when compared to control NZB mice, there were significant alterations in the incidence and onset of anti-erythrocyte antibody levels. NZB.β2m(-/-) had a lower incidence and a delayed onset of anti-erythrocyte autoantibody production compared to that seen in NZB mice. We also compared constitutive and PHA-P- driven levels of IFN-γ, IL-4, IL-6, and IL-12 in cells from NZB, NZB.β2/(- /-), and control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-γ, and a marked increase in IL-6 and IL-12 in NZB and NZB.β2m(-/-) mice.

UR - http://www.scopus.com/inward/record.url?scp=0031239980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031239980&partnerID=8YFLogxK

U2 - 10.1006/clin.1997.4398

DO - 10.1006/clin.1997.4398

M3 - Article

VL - 84

SP - 318

EP - 327

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 3

ER -