Human Type I Interferons Differ Greatly in Their Effects on the Proliferation of Primary B Cells

We examined the effects of eight subtypes of human interferon-alpha (IFN-alpha) and human IFN-beta on primary human B cells. In costimulation with antibodies to IgM (but not to C D40), some of these induced the cells to proliferate (but not to differentiate). Individual IFN differed greatly in their relative proliferative effects. IFN alpha 8 at 0.1-0.5ng/ml induced proliferation, whereas most other subtypes were active only at concentrations 5ng/ml, and IFN-alpha1 was inactive. These marked differences were not due to a selective overall increase in B cell response only to some IFN subtypes, as all those tested similarly induced the IFN-inducible genes 6-16 and HLA class I. Our results show that human B cells must respond to type I IFN via two distinct pathways. One is specific for IFN-alpha8 but can be activated by other IFN at relatively high concentrations. The other responds to them all and causes activation of IFN-inducible genes.