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Publication : Autoantibody production and cytokine profiles of MHC class I (beta2-microglobulin) gene deleted New Zealand black (NZB) mice.

First Author  Chen SY Year  1997
Journal  Clin Immunol Immunopathol Volume  84
Issue  3 Pages  318-27
PubMed ID  9281391 Mgi Jnum  J:42699
Mgi Id  MGI:1096174 Doi  10.1006/clin.1997.4398
Citation  Chen SY, et al. (1997) Autoantibody production and cytokine profiles of MHC class I (beta2-microglobulin) gene deleted New Zealand black (NZB) mice. Clin Immunol Immunopathol 84(3):318-27
abstractText  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.
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