Mechanism of B-cell activation and self-non-self discrimination

The evidence for the one, nonspecific signal hypothesis, which states that the B lymphocytes are activated by nonclonally distributed receptors which are not the Ig receptors, has been summarized. Even though protein A is a polyclonal B-cell activator, it does not exert its effect by interacting with the Fc part of Ig receptors. One consequence of the one, nonspecific signal concept is that thymus-dependent antigens cannot activate or tolerize B cells. It was shown that B cells from animals tolerant to a thymus-dependent protein antigen could be activated by polyclonal B-cell activators to produce antibodies against the tolerogen. Experimentally induced tolerance did not differ from tolerance to self antigens, since LPS and PPD induced autoantibodies capable of lysing autologous red cells and isotope-labeled autologous and syngenic spleen cells. Thus B cells cannot discriminate self from non-self, whereas T cells have been shown to possess this ability.