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RIIa Is Expressed on Natural IFN-
-Producing Cells (Plasmacytoid Dendritic Cells) and Is Required for the IFN- Production Induced by Apoptotic Cells Combined with Lupus IgG 1
* Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden; and
Department of Veterinary Microbiology, Section of Immunology, Swedish University of Agriculture Science, Uppsala, Sweden
An ongoing production of IFN-
may be of etiopathogenic significance in systemic lupus erythematosus (SLE). It may be due to the natural IFN-producing cells (NIPC), also termed plasmacytoid dendritic cells (PDC), activated by immune complexes that contain nucleic acids derived from apoptotic cells. We here examined the role of Fc
R in the IFN- production in vitro by PBMC induced by the combination of apoptotic U937 cells and autoantibody-containing IgG from SLE patients (SLE-IgG). The Fc portion of the SLE-IgG was essential to induce IFN- production, because Fab fragments or F(ab')2 were ineffective. Normal, especially heat-aggregated, IgG inhibited the IFN- production, suggesting a role for FcR on PBMC. Using blocking anti-FcR Abs, the FcRIIa,c (CD32) but not FcRI or FcRIII were shown to be involved in the IFN- induction by apoptotic cells combined with SLE-IgG, but not by HSV or CpG DNA. In contrast, the action of all of these inducers was inhibited by the anti-FcRIIa,b,c mAb AT10 or heat-aggregated IgG. Flow cytometric analysis revealed that 
50% of the BDCA-2-positive PBMC, i.e., NIPC/PDC, expressed low but significant levels of FcRII, as did most of the actual IFN- producers activated by HSV. RT-PCR applied to NIPC/PDC purified by FACS demonstrated expression of FcRIIa, but not of FcRIIb or FcRIIc. We conclude that FcRIIa on NIPC/PDC is involved in the activation of IFN- production by interferogenic immune complexes, but may also mediate inhibitory signals. The FcRIIa could therefore have a key function in NIPC/PDC and be a potential therapeutic target in SLE.
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