Effect of interferon-α on immunoglobulin synthesis by human B cells

We have investigated the effect of human recombinant interferon-α (IFN-α) on mitogen-induced immunoglobulin (Ig) production by peripheral blood mononuclear cells from normal individuals. Low concentrations (1 to 100 IU/ml) of IFN-α enhanced pokeweed mitogen-stimulated Ig production. In contrast, high concentrations of IFN-α (10⁵ IU/ML) suppressed pokeweed mitogen-induced Ig production. Irradiation of T cells did not ablate the high dose suppression, indicating that suppression was not due to a radiation-sensitive T cell. Kinetic experiments revealed that IFN-α needed to be added to 10 day cultures within the first 72 hr for either enhancement or suppression to be noted. Preincubation of purified B cells with IFN-α suppressed Ig production as completely as when unfractionaed mononuclear cells were incubated with IFN-α. On the other hand, preincubation of T cells or monocytes with IFN-α had no effect on subsequent Ig production in reconstituted mononuclear cell cultures. Mitogen-induced proliferation of purified B cells was not affected by IFN-α at any concentration, but Ig production by purified B cells stimulated with Staphylococus aureus Cowan I or anti-μ and B cell differentiation factors responded to IFN-α with low concentration enhancement and high concentration suppression. Studies of Epstein-Barr virus-transformed B cell lines showed that IFN-α caused a similar effect on the CESS line as on peripheral blood B cells, with low dose enhancement and high dose suppression of Ig production. Thus one IFN-α effect is to modulate Ig production, and this appears to be a direct effect on B cells. Combined with the data in the accompanying paper, the effects of IFN-α on B cell funtion are similar in vivo and in vitro.