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.
Cowdery
J S
JS
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Fleming
A L
AL
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018956:CD5 Antigens; D002478:Cells, Cultured; D005260:Female; D007075:Immunoglobulin M / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008811:Mice, Inbred DBA
D015703:Antigens, CD; D018956:CD5 Antigens; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D007371:Interferon-gamma