Derivatized guanine nucleosides: a new class of adjuvant for in vitro antibody responses.

Abstract

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.