PubMed · 70625
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C Jacque, P Davous, N Baumann. 1977-08-20. Circulating immune complexes and multiple sclerosis.. https://doi.org/10.1016/s0140-6736(77)90345-2
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Intravenously applied human IgG has beneficial effects in treating inflammatory diseases, presumably because it has a complement attenuating role. This role of IgG was studied in vitro by following C3 activation and inactivation in sera that were supplemented with exogenous human IgG and incubated with immune aggregates. IgG added at 2 to 10 mg/mL stimulated the physiologic inactivation of C3b-containing complexes twofold to threefold in 20% sera. This, in turn, lowered the overall C3 activation by 28%, as new C3 convertases primarily assembled on C3b-containing complexes. Exogenous IgG (5 mg/mL) also stimulated inactivation of purified C3b2-IgG complexes, whereby their half-life dropped from 3-4 to 1.5 minutes in 20% serum. IgG appeared to act like a modulator of factor H and I because it did not stimulate inactivation of C3b-containing complexes in factor I-deficient serum. Thus, the known partial protection of C3bn-IgG complexes from inactivation by factor H and I was downregulated by high concentrations of IgG. The ability of high doses of IgG to stimulate complement inactivation is a novel regulatory role of IgG. This may be one of the molecular principles for its therapeutic efficacy in treating complement-mediated inflammations.
HIV-1-infected quiescent CD4+ cells harbor the virus in an inactive state until subsequent activation. The possibility that HIV-1 itself and the virus envelope glycoprotein 120 (gp120) might be important agents of this activation was investigated. The present data indicate that binding of heat-inactivated HIV-1 (iHIV-1) to infected resting PBMCs was sufficient to activate NF-kappa B and AP-1, to induce transition from the G0/G1 stage of the cell cycle to the S/G2/M stage, to induce cell surface expression of CD25, to stimulate provirus integration, and to commit cells to produce virus. The cumulative amount of HIV-1 produced by iHIV-1-stimulated cells strictly depended on the concentration of p24gag in the virion preparations used for stimulation. Moreover, virus production was not evidenced in infected resting cells exposed to iHIV-1 previously incubated with soluble CD4 (sCD4), indicating that activation requires a contact between HIV-1 envelope glycoproteins and cell surface CD4. Although soluble gp120 did not stimulate virus production, we found that transition to the S/G2/M stage of the cell cycle, cell surface expression of activation Ags, and virus production were stimulated by cross-linking of CD4 by gp120-anti-gp120 immune complexes. Finally, incubation of gp120-anti-gp120 immune complexes with sCD4 inhibited these effects. These findings suggest that virions and gp120 anti-gp120 immune complexes found in infected patients at all times of infection can stimulate virus production in CD4+ cells harboring HIV-1 in an inducible state.
The ability of Fc gamma R on monocytes and macrophages to enhance presentation of Ab-bound Ag has been well established. In contrast, studies suggest that Fc gamma RII on B cells functions primarily to suppress B cell responses. We found that presentation of tetanus toxoid (TT) by human EBV-transformed B cells was enhanced by 100- to 1000-fold, when TT was targeted to Fc gamma RII on B cells by using a conjugate consisting of TT covalently linked to anti-human Fc gamma RII mAb 41H16. This enhanced presentation could be blocked by mAb 41H16, heat-aggregated human IgG, or anti-MHC Class II mAb. Similarly, multimeric immune complexes composed to TT and anti-TT mAb, SA13, and 9F12 also enhanced presentation of TT. Furthermore, Fc gamma RII on purified human peripheral blood B cells could also enhance Ag presentation. These studies provide the first clear evidence that Fc gamma RII can participate in enhanced Ag presentation by human B cells and suggest that Fc gamma RII has the potential to play a stimulatory role in human B cell responses to Ag-Ab complexes.