The immune response to dextran in BALB/c mice. I. Modification of "thymus-independent" response by the T cell mitogen concanavalin A.
Normal and congenitally athymic mice respond to immunization with dextran, thus indicating that the response is thymus independent. Athymic mice have lower plaque-forming cell (PFC) response than normal mice 3 days after immunization, but similar PFC response as normal mice by 5 days. Seven to 10 days after immunization, athymic mice maintain a high level of PFC response whereas the PFC response declines sharply in normal mice. Concanavalin A (Con A), added at initiation of in vitro culture, enhances the response of spleen cells from primed normal mice. Treatment with methyl-alpha-D-mannoside (MAM), a competitive inhibitor of binding of Con A, immediately after addition of Con A, abolishes the enhancement. Treatment with MAM, 3 to 6 hr after Con A addition, partially blocks the enhancement. The enhancing effect is dependent on the dose of Con A and the duration of in vivo priming before in vitro culture. Con A does not enhance the in vitro PFC response of cells from primed athymic mice. Supernatants from Con A-treated non-primed normal spleen cell cultures enhance the PFC response of "nude" cells, thereby indicating that enhancement by Con A is mediated through a soluble T cell product(s) with no apparent antigen specificity. Hydroxyurea, an inhibitor of DNA synthesis, blocks the enhancement by Con A of cells primed for 1 to 3 days. Release of hydroxyurea block after 19 hr incubation does not restore the PFC response, thereby indicating the responding anti-dextran PFC precursor cells are engaging actively in DNA synthesis. PFC response of primed cells taken at the peak of anti-dextran response (day 5) shows that they are less susceptible to the hydroxyurea block. Con A enhances the PFC response of cells primed for 5 days even in the absence of DNA synthesis.
D000818:Animals; D000917:Antibody Formation; D001667:Binding, Competitive; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003911:Dextrans / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006462:Hemolytic Plaque Technique; D006918:Hydroxyurea / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D008766:Methylmannosides; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013997:Time Factors
D003911:Dextrans; D008766:Methylmannosides; D003208:Concanavalin A; D006918:Hydroxyurea