title: FcR epsilon+ lymphocytes and regulation of the IgE antibody system. III. Suppressive factor of allergy (SFA) is produced during the in vitro FcR epsilon expression cascade and displays corollary physiologic activity in vivo.
abstract: Exposure of lymphoid cells to IgE induces the expression of Fc receptors for IgE (FcR epsilon) and the production of soluble mediators, termed IgE-induced regulants (EIR). Conventional suppressive factor of allergy (SFA) and enhancing factor of allergy (EFA), derived from mouse ascites fluids, both inhibit IgE-induced FcR epsilon expression in vitro in cultures of unfractionated and T cell-enriched, but not B cell-enriched, lymphoid cells. This indicates that the inhibitory activities of both entities are T cell dependent, and distinguishes them from the inhibitory EIRI, which inhibits FcR epsilon induction in the absence of T cells. Moreover, SFA and EFA can be distinguished from one another by differences in the T cell subsets required for the inhibitory activity of each respective mediator on in vitro IgE-induced FcR epsilon expression. Thus, SFA requires the presence of Lyt-1+ T cells, whereas EFA requires the presence of Lyt-2+ T cells. Supernatant fluids from IgE-stimulated unfractionated lymphoid cell cultures suppress in vivo IgE synthesis in mice, indicating that SFA is produced along with the other species of EIR. To define conditions required for SFA production in vitro, EIR-rich supernatant fluids were tested for the presence of SFA by using Lyt-2+ cell-blocked indicator cells in the in vitro FcR epsilon induction assay system (this eliminates the inhibitory activity of EFA). SFA production in vitro by IgE-stimulated lymphoid cells was shown to result from cooperative interactions between B cells and Lyt-1+ T cells. In addition, as observed with the induction of FcR epsilon in general, induction of SFA requires the initial interaction of B cells with IgE, and the release of the B cell-selective EIRB. Once produced, EIRB can directly stimulate Lyt-1+ cells, but not Lyt-2+ cells, to produce SFA. The physiologic significance of the in vitro induction of SFA by the action of EIRB on Lyt-1+ cells was confirmed by the demonstration that EIRB, devoid of detectable SFA, selectively suppressed in vivo IgE synthesis after administration to intact mice. This indicates that EIRB can stimulate resident T cells of irradiated SJL mice to produce SFA. Finally, as shown previously with conventional ascites-derived SFA, the SFA produced in vitro after stimulation of lymphoid cells with IgE is devoid of IgE-binding properties, because its inhibitory effects on in vivo IgE antibody synthesis are not removed by passage over IgE affinity columns.
mesh_terms: D000818:Animals; D000950:Antigens, Ly; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001667:Binding, Competitive; D001798:Blood Proteins / Q000502:physiology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009930:Organic Chemicals; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D011961:Receptors, Fc / Q000096:biosynthesis* / Q000502:physiology; D017455:Receptors, IgE; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; D001798:Blood Proteins; D007166:Immunosuppressive Agents; D009930:Organic Chemicals; D011961:Receptors, Fc; D017455:Receptors, IgE; C011850:immunoenhancing factor; C023051:suppressive factor of allergy; D007073:Immunoglobulin E