Autoantibody production and cytokine profiles of MHC class I (beta2-microglobulin) gene deleted New Zealand black (NZB) mice.
We established a colony of MHC class I deleted (knockout) NZB mice, which lack the beta2 microglobulin gene (NZB.beta2m-/-), 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.beta2m-/-. However, although NZB.beta2m-/- 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.beta2m-/- 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-gamma, IL-4, IL-6, and IL-12 in cells from NZB, NZB.beta-/-2, and control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-gamma, and a marked increase in IL-6 and IL-12 in NZB and NZB.beta2m-/- mice.
Chen
S Y
SY
School of Medicine, University of California at Davis, Davis, California 95616, USA.
Takeoka
Y
Y
Pike-Nobile
L
L
Ansari
A A
AA
Boyd
R
R
Gershwin
M E
ME
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology*; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D005805:Genes, MHC Class I / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013950:Thymus Gland / Q000002:abnormalities; D001613:beta 2-Microglobulin / Q000235:genetics*
D001323:Autoantibodies; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma