Metadata about: The absence of early complement components (C1, C4 and C2 but not C3) is a predisposing factor for systemic lupus erythematosus (SLE). Recently, we demonstrated that, in C4‐deficient (C4 def.) mice, IgM‐containing immune complexes (IgM‐IC) are filtered by the splenic barrier of marginal zone macrophages (MZM), resulting in an increased immune response against antigens within these IgM‐IC, but this could not be observed in wildtype or C3 def. mice. We hypothesized that splenic CD11b(+) MZM play an important role in the induction of autoimmunity, and we therefore analysed their cytokine profile after isolation with the help of magnetic antibody cell sorting. mRNA was isolated, and real‐time PCR was performed with specific primers for murine IFN‐γ (IFN‐γ), interleukin‐12 (IL‐12) and IFN‐α (IFN‐α). We observe a moderate increase of IL‐12 and IFN‐γ mRNA in CD11b(+) cells of C4 def. mice compared to wildtype cells. Surprisingly, the concentration of IFN‐α mRNA is six times higher in C4 def. mice. Preliminary results suggest that mRNA in CD11b(+) cells of C3 def. mice is even lower than that in wt. Six hours following i.v. application of 20 µg of a murine monoclonal IgM anti‐dsDNA antibody, production of IL‐12, IFN‐γ and IFN‐α mRNA is increased in CD11b(+) cells of both C4 def. and wt mice. Several references described increased levels of INF‐α in patients with SLE. Dendritic cells are discussed as a major source of IFN‐α. Our observation that C4‐deficient, SLE‐susceptible mice demonstrate an increased spontaneous IFN‐α production by splenic CD11b(+) marginal zone macrophages could be an early sign and a trigger for the development of SLE. This is supported by the fact that the absence of C3 is not a predisposing factor for SLE and our observation that C3 def. animals display low levels of IFN‐α mRNA.

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