Intravenous immunoglobulin inhibits IgE production in human B lymphocytes

Background: Intravenous immunoglobulin (IVIG) is commonly used as both an immune-enhancing and immune-modulating agent. Treatment with high doses of IVIG diminishes IgE secretion in patients with severe steroid-dependent asthma. Objective: We studied the action of IVIG on IgE production in highly purified B lymphocytes stimulated without additional T cells to determine the action of IVIG on B lymphocytes. Methods: Human B cells were purified from tonsils, and T lymphocytes were removed by E-rosetting. B cells were cultured with IL-4 (400 U/mL) and anti-CD40 antibodies (1 mu g/mL), with or without additional IVIG. Cell proliferation was determined by (3)[H]-thymidine uptake, and supernatant IgE was determined by ELISA, Cell cycle analysis was performed by flow cytometry, and IgE transcripts were measured by in situ hybridization. Results: IVIG (5 mg/mL) decreased B-cell proliferation in IL-4/anti-CD40-stimulated B cells by an average of 74% (+/-6%). Addition of IVIG up to 48 hours after initiation of cell culture led to significant diminution of cell proliferation at 96 to 120 hours. This effect was dose dependent, with 10 mg/mL being the most effective and doses under 0.1 mg/mL having minimal effect. IVIG diminished the number of stimulated cells progressing in the cell cycle by 30%, and there was no difference in cell viability between IVIG-treated and lVIG-untreated cells. The production of IgE in culture by anti-CD40/IL-4-stimulated B lymphocytes was curtailed by greater than 80% after addition of 5 mg/mL IVIG, This was associated with a decrease in IgE (epsilon) transcripts in IVIG-treated cultures. Conclusion: These data indicate that diminution of IgE production in anti-CD40/IL-4-stimulated B cells by IVIG is due to inhibition of early events related to proliferation and progression in the cell cycle.