Derivatized guanine nucleosides: a new class of adjuvant for in vitro antibody responses.
Guanine ribonucleosides, substituted at the C8 position with either a bromine or thiol group, are potent adjuvants when added to culture with antigen. Responses from both naive and antigen-experienced B cells are augmented by the presence of the nucleoside derivatives. Like the induction of B cell proliferation and polyclonal immunoglobulin secretion, enhancement of antibody responses is not attributable to structural analogy between 8BrGuo and the cyclic nucleotide 8Br-cGMP, because the latter compound is unable to augment the antibody response. The capacity of 8MGuo to augment both T-independent and T helper factor-supported antibody responses suggests that the nucleoside acts by directly interacting with B cells and/or antigen-presenting cells. 8MGuo retains its full adjuvant activity even when added 3 days after culture initiation, a time that is too late for freshly added T cells to support a response. Finally, supplementation of cultures of spleen cells from immunodeficient (CBA/N x CBA/CaJ)F1 male mice with the nucleoside effectively restored to normal their capacity to generate an antibody response.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology; D006152:Cyclic GMP / Q000494:pharmacology; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007518:Isoantibodies / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology; D013872:Thionucleosides / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000955:Antigens, T-Independent; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies; D013872:Thionucleosides; D006151:Guanosine; C035169:8-bromoguanosine; C037031:8-thioguanosine; D006152:Cyclic GMP