The capacity of the immune system to respond to an antigenic stimulus with the production of antigen-specific immunoglobulin (Ig) is one of its fundamental properties. Recently, in vitro models of antigen-induced, antigen-specific antibody production have been developed using human peripheral blood mononuclear cells (PBMNC). In the present study, tetanus toxoid (TT), a soluble antigen to which humans are commonly immunized, was used to trigger in vitro antigen-specific antibody synthesis by peripheral blood lymphocytes from subjects recently boosted in vivo to this recall antigen. A sensitive and specific enzyme-linked immunosorbent assay was developed for detecting anti-TT antibody. TT alone, without exogenous mitogen, induced primarily an IgG anti-TT response in vitro. Optimal responses were obtained at the extremely low antigen concentration of 1 ng/ml, concentrations at which little polyclonal Ig production was observed. In contrast, maximum polyclonal Ig synthesis was seen at concentrations of TT greater than 1 µg, levels at which specific anti-TT production was suppressed. Specific anti-TT responses were dependent on the presence of T lymphocytes. Antigen-inducible responses showed significant differences when compared with responses induced by the polyclonal B cell activator, pokeweed mitogen (PWM). T cell help for the antigen-induced specific response was radiosensitive in contrast to T cell help for the PWM-induced responses that were relatively radioresistent. In addition, antigen-inducible anti-TT-specific B cell responses were present in nylon wool T cell fractions, whereas PWM-inducible responses were not found, suggesting the presence of different subpopulations of antigen-specific B lymphocytes in peripheral blood. When stimulatory concentrations of TT were combined with PWM, unexpected suppression of the PWM-inducible responses occurred in some cases, whereas both specific antibody production against another antigen and polyclonal Ig production remained unchanged. Thus, a TT-induced, TT-specific culture and assay system for anti-TT production by human PBMNC has been developed that provides a sensitive and accessible in vitro model for delineating the precise role of antigen in the activation and immunoregulation of specific antibody responses in man.
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Volkman et al. (1982) studied this question.