Examination of the Inhibitory and Stimulatory Effects of IFN-Alpha, -Beta, and -Gamma on Human B-Cell Proliferation Induced by Various B-Cell Mitogens

摘要

Interferons are a family of proteins and glycoproteins with known anti-viral, anti-proliferative, and immunoregulatory activities, In order to compare the actions of interferons on the various pathways leading to human B-cell activation, we examined the effects of alpha-interferon (INF-alpha), Beta-interferon (INF-Beta), and gamma-interferon (INF-gamma) on B-cell responses to mitogenic stimuli which differ in their mode of B-cell stimulation. Utilizing highly purified small, dense peripheral blood B-cells or splenic lymphocytes, we demonstrate that (i) INF-alpha, Beta, and gamma enhance human B-cell proliferation induced by cross-linking of surface Ig with either SAC or anti-mu in a dose-dependent fashion, analogous to and with a magnitude equal to or greater than that seen with human B-cell growth factor; (ii)INF-alpha and Beta, but not IFN-gamma inhibit phorbol myristate acetate-mediated B-cell mitogenesis, again in a dose-dependent manner; and (iii) IFN-gamma does not effect B-cell cytoplasmic calcium (CA2+i) influx, either in the resting state or following stimulation with anti-mu, making it unlikely that IFN-gamma exerts its stimulatory effects on B-cell function through changes in (Ca2+)i. Taken together, these findings suggest that all three types of interferons may have important immunoregulatory roles in B-cell activity, and that their ability to enhance or suppress B-cell activation depends on the nature of the mitogenic stimulus. Reprints. (AW)