Functional Defects of Culture-Grown Bone Marrow-Derived Macrophages from Autoimmune MRL/MpJ-1pr/1pr Mice

Abstract

To investigate the primary defects and development of macrophages in MRL/MpJ-1pr/1pr (MRL/1) mice, we used a pure population of macrophages derived from bone marrow precursor cells cultured in the presence of L-cell conditioned medium (LCM) as a source of colony stimulating factor. Bone marrow-derived macrophages (BMMφ) from MRL/1 mice had lower antigen presenting activity as detected by the induction of antigen-specific T cell prolifei ation, than age- and sex-matched control mice (CBA/J). Cell surface antigens (Ia and Mac-1) were determined quantitatively by a cell sorter as markers of macrophage differentiation. The BMMφ from MRL/1 contained a much smaller number of Ia antigen-positive macrophages than those from normal mice. Treatment of BMMφ with an Ia-inducing of factor (IFN-γ) markedly increased the expression of Ia antigens. This increase was significantly greater in BMMφ from MRL/1 mice than in BMMφ from control mice. Expression of Mac-1 antigen was not different in BMMφ from the two strains. The Fc-mediated phagocytosis of IgG-coated sheep red blood cells was decreased in BMMφ from MRL/1 mice compared with those from control mice. The function of nonspecific phagocytosis as measured by latex-bead incorporation was also impaired in MRL/1 mice. The functional defects of MRL/1 BMMφ found in these experiments are not secondary defects acquired under the influence of environmental signals during development, but are derived from the primary abnormalities which already exist in myeloid stem cells.