Prostaglandin E2 modulation of rheumatoid factor synthesis.
We examined the influence of prostaglandin E2 (PGE2) on the in vitro synthesis of rheumatoid factor (RF) by purified human B and T lymphocytes stimulated with Staphylococcus aureus Cowan 1 or pokeweed mitogen (PWM). Supernatants were assayed for total IgM and RF. PGE2 at concentrations of 10(-7) M to 10(-9) M significantly inhibited RF and IgM secretion stimulated by S aureus Cowan 1, a cross-linker of B cell surface Ig. The magnitude of inhibition of RF production was significantly greater than that of total IgM at low PGE2 concentrations (P less than 0.05). In contrast, PWM-stimulated cultures were only minimally inhibited by PGE2 at all concentrations tested. Since cross-linking of surface Ig renders B cells more susceptible to inhibition by PGE2, heat-aggregated IgG (HAIgG) was added to the PWM-stimulated cultures in an attempt to increase the sensitivity of precursors of RF-secreting cells to the inhibitory effects of PGE2. Addition of HAIgG markedly increased PGE2-mediated inhibition of RF synthesis without significantly affecting IgM production. Inhibition could not be overcome by the addition of soluble T helper cell factors, indicating that PGE2-mediated suppression was not the result of an inhibitory action of T helper cells. When lymphocytes from patients with rheumatoid arthritis were examined, HAIgG was found to be unable to induce sensitivity to PGE2-mediated inhibition of responsiveness. These results suggest that down-regulation of RF synthesis requires both cross-linking of surface Ig and the influence of PGE2. Abnormalities in this immunoregulatory mechanism may explain the ongoing production of RF in patients with rheumatoid arthritis.
Alvarellos
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A
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235-9030.
Lipsky
P E
PE
Jasin
H E
HE
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015232:Dinoprostone / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D007075:Immunoglobulin M / Q000096:biosynthesis*; D066298:In Vitro Techniques; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011863:Radioimmunoassay; D012217:Rheumatoid Factor / Q000096:biosynthesis*; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011043:Pokeweed Mitogens; D012217:Rheumatoid Factor; D015232:Dinoprostone