title: The role of nonactivated and interferon-gamma activated monocytes in regulating normal and SLE patient B cell responses to TNP-Brucella abortus.
abstract: We have previously characterized the human B cell response to trinitrophenol (TNP)-Brucella abortus (Ba) response as being T cell independent. In this report we examine the role of monocytes in the TNP-Ba antibody response of human peripheral blood mononuclear cells (PBMC). Depletion of monocytes by sequential adherence to plastic and Sephadex G-10 passage did not result in decreased plaque-forming cell responses to TNP-Ba, suggesting that monocytes were not required. On the contrary monocytes were probably inhibitory because their removal resulted in enhanced responses. This was confirmed by showing that adding monocytes back reconstituted the inhibition. When interferon-gamma (IFN-gamma), a potent activator of monocytes, was added to TNP-Ba-driven PBMC cultures, marked inhibition (greater than 90%) of the responses ensued. This IFN-gamma-mediated suppression was monocyte dependent because it was completely abrogated by monocyte, but not T cell depletion. Previously, we described a concanavalin A (Con A), T cell inhibition pathway of the TNP-Ba response. Both the Con A and IFN-gamma pathways were tested for their ability to inhibit systemic lupus erythematosus (SLE) patient responses to TNP-Ba. The B cell response of SLE patients was inhibitable by both pathways. In all of the patients, the inhibition was complete (greater than 95%) when IFN-gamma was added to the cultures. In the presence of Con A, greater than 95% inhibition was observed in six of 10 patients, the remainder being inhibited to a lesser extent. Thus the hyperactive B cells from SLE patients can be down-regulated, particularly in the presence of IFN-gamma.
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive; D002003:Brucella abortus / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D006462:Hemolytic Plaque Technique; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009578:Nitrobenzenes / Q000276:immunology*; D011453:Prostaglandins / Q000378:metabolism; D014301:Trinitrobenzenes / Q000276:immunology*
chemical_list: D009578:Nitrobenzenes; D011453:Prostaglandins; D014301:Trinitrobenzenes; D003208:Concanavalin A; D007371:Interferon-gamma