Soluble FcR Block Suppressor T Cell Activity at Low Concentrationin VitroAllowing Isotype-Specific Antibody Production
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abstract
IgA and IgG binding factors (BF) can be found in the supernatant (Th sup) of cultures containing macrophages and CD4+ T cells stimulated with particulate antigens such as SRBC. Previous work indicated that these IgBF, when mixed with normal serum immunoglobulin, could block the activity of suppressor T cells (Ts) and allow IgA and IgG PFC responses in vitro. We present serologic and functional evidence that IgABF and IgGBF in Th sup are soluble Fc alpha R and Fc gamma RII (or III), respectively. Th sup adsorbed on affinity columns containing anti-Fc gamma RII/III mAB or murine IgG failed to augment IgG PFC responses. Material eluted from either the IgG or anti-Fc gamma RII/III columns could be added back, interchangeably, to the adsorbed Th sup and restore IgG PFC. Recombinant murine Fc gamma RII(rFc gamma RII), added to the same adsorbed Th sup at 0.01 to 0.5 ng/ml, resulted in a similar augmentation of IgG PFC. Interestingly, much higher concentrations of rFc gamma RII (10-100 ng/mL) could not augment IgG PFC responses. Protein dot blots showed that Th sup and the eluted material from murine IgG columns contained structures reactive with the Fc gamma RII/III mAb. Similar studies using purified Fc alpha R revealed that IgABF eluted from IgA or anti-Fc alpha R revealed that IgABF eluted from IgA or anti-Fc alpha R columns was in fact Fc alpha R. Cross-adsorption studies indicated clearly that the IgGBF (Fc gamma RII/III) and the IgABF (Fc alpha R) were separate molecules produced in the same Th sup and that each regulated their respective Ig isotype independently. Thus, cultures of splenic macrophage and CD4+ T cells, in the presence of particulate antigens such as SRBC, generate both Fc gamma RII/III and Fc alpha R. This soluble FcR in combination with serum Ig act to block isotype specific Ts cells at low concentration in vitro.
