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J Inherit Metab Dis. 2012 Jan;35(1):159-68. doi: 10.1007/s10545-011-9349-x. Epub 2011 May 24.

Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase-deficient mouse model of human hyper-IgD syndrome (HIDS).

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  • 1Department of Biological Sciences, DOW ESE Room 742, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA.



We sought to determine the activation status and proliferative capacities of splenic lymphocyte populations from a mevalonate kinase-deficient mouse model of hyper-IgD syndrome (HIDS). We previously reported that murine mevalonate kinase gene ablation was embryonic lethal for homozygous mutants while heterozygotes (Mvk (+/-)) demonstrated several phenotypic features of human HIDS including increased serum levels of IgD, IgA, and TNFα, temperature dysregulation, hematological abnormalities, and splenomegaly.


Flow cytometric analysis of cell surface activation markers on T and B lymphocytes, and macrophage populations, demonstrated aberrant expression of B7 glycoproteins in all splenic cell types studied. Differences in expression levels between Mvk (+/-) and Mvk (+/+) littermate controls were observed in both the basal state (unstimulated) and after Concanavalin A (Con-A) stimulation in vitro of whole splenocyte cultures. In Mvk (+/-) CD4 and CD8 T cells, alterations in expression of CD25, CD80, CD152, and CD28 were observed. Mvk (+/-) splenic macrophages expressed altered levels of CD80, CD86, CD40, and CD11c while Mvk (+/-) B lymphocytes had differential expression of CD40, CD80, and CD86. Mvk (+/-) splenocyte subpopulations also exhibited altered proliferative capacities in response to in vitro stimulation.


We postulate that imbalances in the expression of cell surface proteins necessary for activation, proliferation, and regulation of the intensity and duration of an immune response may result in defective T cell activation, proliferation, and effector functions in our model and potentially in human HIDS.

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