In vivo depletion of CD4 T cells increases B cell sensitivity to polyclonal activation: the role of interferon-gamma.

Chronic in vivo depletion of CD4+ T cells results in a marked increase in serum IgM levels. When normal mice were acutely depleted of CD4+ T cells, unfractionated spleen cell cultures showed an increased sensitivity to lipopolysaccharide (LPS)-induced IgM secretion. Sensitivity to LPS-induced proliferation was similar in both control cultures and cultures from CD4-depleted donors. When exogenous recombinant murine interferon-gamma (IFN-gamma) was added to spleen cell cultures from CD4-depleted donors, the sensitivity to LPS-induced IgM secretion was restored to the level seen in spleen cell cultures from control animals. IFN-gamma did not influence the proliferative response of purified B cells to LPS but was capable of profoundly inhibiting the LPS-induced differentiation of purified B cells. Thus the effect of IFN-gamma was anti-differentiative and was exerted directly on the B cell. Finally, the LPS-induced differentiation of normal spleen cells was enhanced in the presence of mAb directed against IFN-gamma. These findings illustrate that IFN-gamma plays a key role in regulating the B cell compartment response to LPS-induced differentiation. The hyper-IgM syndrome seen in association with CD4 T cell depletion may be due to a loss of in vivo production of IFN-gamma.