INTRAVENOUS IMMUNOGLOBULINS SUPPRESS IMMUNOGLOBULIN PRODUCTIONS BY SUPPRESSING CA2-DEPENDENT SIGNAL-TRANSDUCTION THROUGH FC-GAMMA RECEPTORSIN B-LYMPHOCYTES()

A high dose intravenous immunoglobulin (IVIG) therapy is used in the t reatment of a wide range of autoimmune disorders. However, the mechani sms of the action of IVIGs remain poorly understood. To analyse the me chanisms of effects of IVIGs on immunoglobulin (Ig) production of B ce lls, the effects of IVIGs on B lymphoblastoid cell lines transformed b y Epstein-Barr virus (LCLs) were investigated. The productions of IgG or IgM of LCLs were dose-dependently suppressed by polyethylene glycol (PEG)-treated IVIG or pH 4-treated IVIG though the productions were n ot or only slightly suppressed by pepsin-treated IVIG. The suppression by IVIGs was blocked by anti-human IgG Fc or anti-Fc gamma RII. C mu gene expression and mu s C terminal gene expression of LCLs were suppr essed by PEG-treated IVIG, whereas neither C mu gene expression nor mu s C terminal gene expression of LCLs were suppressed by pepsin-treate d IVIG. Although the increase in intracellular calcium concentration i n LCLs was not suppressed by pepsin-treated IVIG, the increase was sup pressed by PEG-treated IVIG. This suppressing effect of PEG-treated IV IG on intracellular calcium concentration of LCLs was blocked by anti- human IgG Fc or anti- Fc gamma RII. Our results suggest that IVIGs sup pressed the Ca2+-dependent signal transduction through Fc gamma R on B -cell membrane, consequently, the transcription of C mu mRNA, especial ly secreted mu mRNA was suppressed in the B cells.