Greatly accelerated lymphadenopathy and autoimmune disease in lpr mice lacking tumor necrosis factor receptor I.

Zhou, Tong; Edwards, Carl K.; Yang, PingAr; Wang, Zheng; Bluethmann, Horst; Mountz, J D

doi:10.4049/jimmunol.156.8.2661

Cited by 142 publications

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“…This accelerated autoimmune disease in the CK2␣ transgenic lpr/lpr mice differs from the reports on the bcl-2 transgenic lpr/lpr mice (42) and the pim-1 transgenic lpr/lpr mice (43), where no enhancement of autoantibody production or increase in serum Ig was observed. Loss of the TNF receptor type I induced both accelerated lymphoproliferation and autoimmunity but not lymphoma (44), much as we see with overexpression of CK2␣.…”

Section: Discussionsupporting

confidence: 73%

Acceleration oflprLymphoproliferative and Autoimmune Disease by Transgenic Protein Kinase CK2α

Rifkin

Channavajhala

Kiefer

et al. 1998

The Journal of Immunology

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MRL-lpr/lpr mice have a Fas receptor mutation that leads to abnormalities of apoptosis, lymphoproliferation, and a lupus-like autoimmune disease associated with the production of autoantibodies. Other than Fas pathway defects, little is known about molecular abnormalities that predispose to autoimmunity. Protein kinase CK2 (also termed casein kinase II), a serine-threonine protein kinase whose targets include many critical regulators of cellular growth, is highly expressed in a lymphoproliferative disease of cattle and in many human cancers. Overexpression of the CK2α catalytic subunit in lymphocytes of transgenic mice leads to T cell lymphoma. We hypothesized that CK2 dysregulation and Fas mutation might cooperatively augment lymphocyte proliferation and transformation. We find that in MRL-lpr/lpr mice bearing the CK2α transgene, the lymphoproliferative process is dramatically exacerbated, as these mice develop massive splenomegaly and lymphadenopathy by 12 wk of age in association with increased autoantibody production and accelerated renal disease. The lymphoid organs are filled with the unusual B220+CD4−CD8− T cells typically seen in MRL-lpr/lpr mice, not the B220−CD4+CD8+ or B220−CD4−CD8+ T cells typically seen in CK2α transgenic lymphomas. The T cells do not fulfill the criteria for transformation, as they are polyclonal and not transplantable or immortal in cell culture. Thus, although the lpr lymphoproliferative and autoimmune syndrome is potentiated by the presence of the CK2α transgene, this combination of apoptotic and proliferative abnormalities appears to be insufficient to transform lymphoid cells.

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Section: Discussionsupporting

confidence: 73%