Functional heterogeneity of culture-grown bone marrow-derived macrophages. II. Lymphokine stimulation of...

The activation of immunostimulatory activity and Ia expression was studied in pure populations of murine macrophages (M phi) grown in vitro from bone marrow precursor cells in the presence of L cell-conditioned medium as the source of colony-stimulating factor. During exponential growth, the M phi developed maximal Ia-dependent antigen-presenting activity as detected by the induction of antigen-specific T cell proliferation, but the proportion of Ia+ M phi was low (less than 10%). Fractionation of the M phi according to size by velocity sedimentation resulted in concentration of the antigen-presenting cells in the smallest fraction, but the enrichment of Ia+ M phi in this fraction was less than twofold. All fractions also showed comparable degrees of antigen uptake regardless of their T cell-stimulating activity. Thus Ia and antigen, although obviously essential, are insufficient for full manifestation of antigen-presenting function. Activation of M phi with lymphokines from Mycobacterium-activated lymph node cells resulted in enhanced Ia expression in all fractions, but only small M phi showed an enhancement in antigen presentation. Large activation M phi were found to exert an immunosuppressive effect that probably neutralized any augmentation of stimulatory activity. thus heterogeneity can be demonstrated in i) the function of unstimulated M phi, ii) the responsiveness of subsets to stimulation, and iii) the manifestation of activated functions.