Suppression of immunoglobulin production of lymphocytes by intravenous immunoglobulin

Abstract

The proliferative responses and the immunoglobulin production of peripheral blood mononuclear cells to pokeweed mitogen were dose-dependently suppressed by sulfonated intravenous immunoglobulin (IVIG), polyethylene glycol-treated IVIG, pH 4-treated IVIG, or human gamma-globulin, but they were not or only slightly suppressed by human serum albumin or pepsin-treated IVIG. Moreover, the suppression of immunoglobulin production by sulfonated IVIG, polyethylene glycol-treated IVIG, or pH 4-treated IVIG was seen in the cases in which B cells preincubated with IVIGs were cocultured with T cells and monocytes preincubated with or without IVIGs and in the cases in which monocytes preincubated with IVIGs were cocultured with T cells and B cells preincubated with or without IVIGs. However, in the cases in which only T cells were preincubated with IVIGs, immunoglobulin production was not suppressed. The suppression of the monocyte function by IVIGs tended to be less than the suppression of the B-cell function by IVIGs. Moreover, the suppression by IVIGs was blocked by anti-human IgG Fc. Our results suggest that IVIGs suppress the immunoglobulin production of lymphocytes through suppression of the B-cell function and the antigen presenting-cell function by attachment of IVIGs to Fc receptors of B-cell membranes and antigen presenting-cell membranes.

Suppression of allo-human leucocyte antigen (HLA) antibodies secreted by B memory cellsin vitro: intravenous immunoglobulin (IVIg) versusa monoclonal anti-HLA-E IgG that mimics HLA-I reactivities of IVIg

“…Our observations, therefore, suggest that the findings of dose-dependent suppression by IVIg may not have been due to direct interaction with B cells. As other groups [28,29] have reported, the observed suppression of allo-HLA antibody production in vivo by modified IVIg [26] could be due to suppression of T cell proliferation, activation or antigen presentation.…”

Neutralization of mitogenic lectins by intravenous immunoglobulin (IVIg) prevents T cell activation: does IVIg really have a direct effect on T cells?

“…These lectins have been used in numerous studies to determine the effect of IVIg on lymphocyte functions, leading to the conclusion that IVIg had a direct effect on activated T or B cells (inhibition of proliferation, cytokine secretion, expression of activation markers such as CD25 or CD69, or immunoglobulin secretion) [22][23][24][25][26][27][28][29]. In the light of the results presented here, we believe that these conclusions should be revisited.…”

30 years of Immunomodulation by Intravenous Immunoglobulin

“…On B cells: neutralization of specific autoantibodies by anti-idiotypic antibodies of IVIG, downregulation of autoantibody production [12,13] and neutralization of B-cell survival and activating factors such as BAFF and the proliferation-inducing ligand APRIL [14]. [15], cytokine release and increases Tregs [16].…”