Regulation of the immune system by synthetic polynucleotides. V. Effect on cell-associated immunoglobulin receptors and immunological memory.
Addition of polyadenylic-polyuridylic acid in complex form (poly A:U) without antigen to a suspension of spleen cells obtained from BALB/Aj mice primed 6 wk previously with human gamma-globulin (HGG) resulted in an immediate fourfold increase over background number of anti-HGG rosette-forming cells (RFC). Culture of similar cells in the presence of puromycin for 1-6 hr before poly A:U did not significantly reduce the response. Continued culture of primed spleen cells in the presence of poly A:U, resulted in a decrease of RFC to background levels within an hour followed by an increase again 6 hr later. This later increase in RFC was inhibited by addition of puromycin to the culture medium. The nonspecific stimulation by poly A:U of antibody production by primed spleen cells also was induced in vivo. Increases in splenic RFC were detectable 6 hr after intravenous injection of poly A:U alone, without antigen, into primed mice. The response peaked at 18 hr and had dissipated completely within 3 days. A second injection of poly A:U 24 hr or later after the first injection resulted in a second response, similar to the first with respect to kinetics and intensity. Rosette formation by poly A:U-stimulated cells could not be inhibited by mitotic poisons, but was inhibited by treatment of the cells with goat anti-mouse gamma-globulin serum, suggesting that the antibody involved was a 7S gamma-globulin. The decrease in RFC induced by culture of primed cells for 1 hr in poly A:U paralleled a decrease in secondary responsiveness of the cells to antigen. This poly A:U-induced inhibition of secondary responsiveness could be reversed by suspending the treated cells in supernatant fluids derived from poly A:U-stimulated cultures. The reversal was specific in that supernatant fluids removed from bovine serum albumin (BSA)-primed cells by poly A:U did not stimulate the response of HGG-primed cells to HGG. However supernatant fluids from BSA-primed cells caused the production of anti-HGG RFC if BSA rather than HGG was used as triggering antigen. The active factor in the supernatant fluids appeared to be a 7S gamma-globulin since activity was lost after 45 min incubation of the supernatant fluids in the presence of goat anti-mouse 7S gamma-globulin serum.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D002628:Chemoreceptor Cells; D007111:Immunity, Cellular / Q000187:drug effects*; D007074:Immunoglobulin G / Q000494:pharmacology; D007136:Immunoglobulins / Q000494:pharmacology; D007156:Immunologic Memory / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D011119:Polynucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D011691:Puromycin / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects; D005719:gamma-Globulins / Q000494:pharmacology
D007074:Immunoglobulin G; D007136:Immunoglobulins; D011119:Polynucleotides; D005719:gamma-Globulins; D011691:Puromycin