Intravenous immunoglobulins suppress immunoglobulin productions by suppressing Ca(2+)-dependent signal transduction through Fc gamma receptors in B lymphocytes.
A high dose intravenous immunoglobulin (IVIG) therapy is used in the treatment of a wide range of autoimmune disorders. However, the mechanisms of the action of IVIGs remain poorly understood. To analyse the mechanisms of effects of IVIGs on immunoglobulin (Ig) production of B cells, the effects of IVIGs on B lymphoblastoid cell lines transformed by 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 not 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 suppressed by PEG-treated IVIG, whereas neither C mu gene expression nor mu s C terminal gene expression of LCLs were suppressed by pepsin-treated IVIG. Although the increase in intracellular calcium concentration in LCLs was not suppressed by pepsin-treated IVIG, the increase was suppressed by PEG-treated IVIG. This suppressing effect of PEG-treated IVIG on intracellular calcium concentration of LCLs was blocked by anti-human IgG Fc or anti- Fc gamma RII. Our results suggest that IVIGs suppressed the Ca(2+)-dependent signal transduction through Fc gamma R on B-cell membrane, consequently, the transcription of C mu mRNA, especially secreted mu mRNA was suppressed in the B cells.
Kondo
N
N
Department of Pediatrics, Gifu University School of Medicine, Japan.
Kasahara
K
K
Kameyama
T
T
Suzuki
Y
Y
Shimozawa
N
N
Tomatsu
S
S
Nakashima
Y
Y
Hori
T
T
Yamagishi
A
A
Ogawa
T
T
D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015152:Blotting, Northern / Q000379:methods; D002118:Calcium / Q000502:physiology*; D002461:Cell Line, Transformed; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D008969:Molecular Sequence Data; D012333:RNA, Messenger; D017452:Receptors, IgG / Q000502:physiology*; D012709:Serum Albumin / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D012333:RNA, Messenger; D017452:Receptors, IgG; D012709:Serum Albumin; D002118:Calcium