Differential responses to mitogen stimulation in lymphocytes from normal individuals and Lesch-Nyhan patients: influence of the bicarbonate buffer system.
Three patients affected with the Lesch-Nyhan syndrome were found to have normal levels of immunoglobulins, normal numbers of circulating B and T cells and normal IgG secretion in vitro in response to polyclonal activators. However, when cultures were performed in the absence of a bicarbonate buffer system, the proliferative response to several T cell stimulants (phytohaemagglutinin, concanavalin A and streptokinase-streptodornase) was impaired in Lesch-Nyhan cells as judged from the incorporation of labelled thymidine, uridine and leucine. This situation could be abolished by incubation in a 5% CO2 atmosphere and even reversed by supplementation of bicarbonate to the culture medium. Blocking the de novo purine synthesis by Methotrexate resulted in a more pronounced inhibition of the mitogenic response in Lesch-Nyhan lymphocytes than in normal cells. The differences in proliferative response between normal and Lesch-Nyhan lymphocytes with regard to culture conditions point to the critical role of the de novo pathway in lymphocyte stimulation.
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D001639:Bicarbonates / Q000494:pharmacology*; D002648:Child; D006801:Humans; D007926:Lesch-Nyhan Syndrome / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects; D008727:Methotrexate / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D013299:Streptodornase and Streptokinase / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D001639:Bicarbonates; D008934:Mitogens; D013299:Streptodornase and Streptokinase; D008727:Methotrexate