Pooled human gammaglobulin modulates surface molecule expression and induces apoptosis in human B cells

We have previously shown that the pooled human gammaglobulin (IVIG) inhibited mixed lymphocyte reaction (MLR). In this study, we examined (1) if IVIG contains blocking antibodies reactive with cell surface molecules required for alloantigen recognition and (2) if IVIG modulates these surface molecule expressions using flow cytometry. IVIG does not contain significant amounts of blocking antibodies against CD3, CD4, CD8, CD20, CD14, CD40, MHC class I and class II. It reduces the number of intact B cells and monocytes, reduces or modulates CD19, CD20 and CD40 expression on B cells, and induces morphological changes in B cells. This B-cell modulation results primarily because of apoptosis. IVIG also induces apoptosis in T cells and monocytes, but to a lesser degree. Induction of apoptosis requires the intact IgG molecule. Reduction of intact B cell and monocyte cell numbers, modulation of surface molecule expression on B cells, and deletion of B and T cells by apoptosis could result in inhibition of optimal T-cell activation. This likely represents the primary mechanism responsible for IVIG suppression of the MLR, and may account for many of the observed beneficial effects of IVIG seen in the treatment of human autoimmune and alloimmune disorders.