Interferon-γ Regulation of B Lymphocyte Differentiation: Activation of B Cells Is a Prerequisite for IFN-γ-Mediated Inhibition of B Cell Differentiation

The Th1 and NK cell-derived cytokine interferon-γ (IFN-γ) influences both immune and inflammatory responses, and under some circumstances, IFN-γ can inhibit B cell differentiation. We found that IFN-γ inhibited LPS-induced IgM production in B cells by reducing the precursor frequency of IgM-secreting cells. This occurred without a significant decrease in B cell proliferation in response to either LPS or F(ab′)2 anti-IgM. We also found that IFN-γ inhibited IgM secretion, even when added as late as 48 hr after LPS stimulation. Small resting B cells were not affected by a pulse with IFN-γ. However, a pulse of IFN-γ inhibited the response of activated B cells to subsequent stimulation with LPS. Also, LPS upregulated expression of the IFN-γ receptor on B cells. Our studies show that IFN-γ targets stimulated but not resting B cells and suggest that IFN-γ plays an important role in the normal homeostatic control of B cell polyclonal responses.