Lack of Fcγ-receptors increases circulating immune complexes but delays development of tissue immune complex deposits
(English)Manuscript (preprint) (Other academic)
Inorganic mercury (Hg) induces in susceptible mouse strains a T-cell dependent, systemic autoimmune condition (HgIA) characterized by immunostimulation, antinuclear antibodies, and immune-complex (IC) deposits in glomeruli and vessel walls. Activating Fcγ-receptors (FcγRs) are important for induction of HgIA. We have examined if activating FcγRs affect circulating immune complexes (CIC), the initial development of tissue IC deposits and their composition in HgIA. BALB/c mice with a targeted mutation for activating FcγRs and BALB/c mice without any mutation (wild type - wt - mice) were treated up to 35 days with Hg. Wild type mice showed a significant but modest increase of CIC from day 12 until day 18 and day 35 for IgG2a- and IgG1-containing CIC, respectively. Mercury-treated FcγR−/− mice showed significantly higher CIC levels than Hg-treated wt mice during the entire treatment time for IgG1-CIC, and after 26 and 35 days for IgG2a-CIC. Tissue IC deposits developed later in the FcγR−/− mice especially in the renal mesangium. After 35 days of Hg treatment the fraction of mice with and/or the amount of IgG1 and C3c deposits were significantly reduced in vessel walls and for IgG1 also in the renal mesangium compared with wt mice. We conclude that susceptible mice lacking activating FcγRs respond to an autoimmune stimulus with increased levels and altered quality of CIC compared with wt mice. It is likely that lack of FcγRs reduced elimination of CIC as indicated by delayed and significantly reduced IC deposits in the tissues of mice without activating receptors.
Mercury, FcγR, CIC, autoimmunity, mice
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-19158OAI: oai:DiVA.org:liu-19158DiVA: diva2:223459