Abstract
The antigen-specific primary antibody response of human lymphocytes in vitro was studied with respect to dependency upon interleukin 2 (IL-2) and subsequent modulation by C8-substituted guanine ribonucleosides. The specific response to sheep erythrocytes was shown to be dependent upon IL-2. Addition of optimal concentrations of the nucleoside, 7-methyl-8-oxoquanosine (7m8oGuo), to cultures containing antigen and IL-2, caused marked amplification of the underlying antibody response. Synergy between 7m8oGuo and IL-2 was antigen-dependent and could not be accounted for by the independent antigen-specific and nonspecific components. That IL-2 itself was responsible for both the specific response to antigen and synergy with 7m8oGuo was confirmed by use of recombinant IL-2. 7m8oGuo enhanced the response to antigen in a dose-dependent fashion. Kinetic studies demonstrated that this nucleoside acts in the context of an ongoing immune response, because its addition could be delayed up to 3 days without loss of activity. The ability of 7m8oGuo to bypass the requirement for intact T cells in this response was substantiated by investigating the ability of B cell-enriched populations to respond to the T-dependent antigen, SRBC, in the presence and absence of 7m8oGuo. T cell-depleted populations were capable of responding to antigen in the presence of 7m8oGuo so long as IL-2 was also present. These data demonstrate that a simple nucleoside analog can amplify the human antibody response in an antigen-specific manner and may act as an alternate source of T cell help.
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Goodman, M., Weiqle, W. ANTIGEN-SPECIFIC ENHANCEMENT OF THE HUMAN ANTIBODY RESPONSE BY A SUBSTITUTED NUCLEOSIDE: 71. Pediatr Res 19, 755 (1985). https://doi.org/10.1203/00006450-198507000-00091
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DOI: https://doi.org/10.1203/00006450-198507000-00091