Osteopetrosis in microphthalmic (mi) mice is characterized by excessive skeletal mass and reduced bone resorption. The skeletal defects can be corrected by the transfer of mononuclear spleen cells from normal httermates. These studies suggest that osteopetrotic mutants might also demonstrate defective immune functions. Several laboratories have demonstrated significantly reduced responses to T and B cell mitogens by spleen cells from mi and op mice and op, osteopetrotic, rats. The problem with these latter studies is that different populations of cells have been compared in mutants and normal littermates because the spleen is a focus of extramedullary hemopoiesis in osteopetrotic animals. To circumvent this problem, cellular suspensions of mononuclear cells from the spleen and mesenteric lymph node were separated using Ficoll-Hypaque from mi and normal littermates 5 and 10 weeks of age. Under appropriate culture conditions these cells were exposed to different concentrations of concanavalin A, phytohemagglutinin and lipopolysaccharide for 3 days and 3H-thymidine for the last 24 h. In all cases, the response to optimal concentrations of the three mitogens was higher for the mi lymph node cells than controls. Contrary to previous studies, the spleen cell response to all three mitogens was only slightly lower in the mi cultures. The cellular composition of the lymph node and spleen samples tested in the mitogen assays was also evaluated by fluorescence microscopy using FITC-conjugated monoclonal antibodies directed against specific cell surface markers. The percentage of B cells, monocytes and macrophages, total T cells, and suppressor/cytotoxic T cells was found to be similar in mi and normal mice using Ficoll-Hypaque isolates of spleen and lymph nodes. These results indicate a normal or slightly enhanced immune function in the mi mutant when similar cell populations are compared.

Keywords:
Immune response, Immunological competence, Bone disease, Osteopetrosis, Bone resorption, Mitogens
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© 1983 S. Karger AG, Basel
1983
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