IFN-gamma is a potent inducer of Ig secretion by sort-purified murine B cells activated through the mIg, but not the CD40, signaling pathway

IFN-gamma has been shown to either stimulate or inhibit Ig secretion, No studies have yet addressed the basis for these seemingly conflicting properties nor whether IFN-gamma acted directly at the level of the B cell to mediate its effects, Thus, we studied the ability of IFN-gamma to regulate Ig secretion in sort-purified, resting murine B cells that were >99% Ig(+), activated either through membrane Ig using unconjugated or dextran-conjugated anti-IgD antibodies (as-dex) or through CD40 using soluble or membrane CD40 ligand (CD40L), B cells activated with alpha delta-dex proliferate but do not secrete Ig, even in the presence of IL-l + IL-2, We demonstrate that IFN-gamma only when added subsequent to B cell stimulation with alpha delta-dex, but not unconjugated anti-IgD antibody, plus IL-l + IL-2 induces up to 100-fold enhancements in Ig secretion and in the numbers of Ig-secreting cells, The predominant Ig isotype secreted is IgM, with IgG3 and IgG2a comprising the majority of non-IgM antibody, IFN-gamma must act in concert with IL-2 for stimulation of Ig secretion, Further, IFN-gamma synergizes with IL-3 + granulocyte-macrophage colony stimulating factor for induction of Ig synthesis, IFN-gamma also enhances IgA synthesis by transforming growth factor-beta-induced membrane IgA(+) cells, By contrast, IFN-gamma fails to stimulate Ig secretion in B cells activated with CD40L in the presence or absence of IL-l + IL-2 or IL-4, However, the combination of CD40L and alpha delta-dex is strongly synergistic for IFN-gamma-induced Ig secretion, Thus, these data establish that IFN-gamma can act directly on the B cell to induce Ig synthesis without the participation of any other cell and demonstrates that the mode of activation of the B cell plays an important role in directing the action of IFN-gamma.