Mechanism of activation of the bone marrow-derived lymphocyte. 3. A distinction between a macrophage-produced triggering signal and the amplifying effect on triggered B lymphocytes of allogeneic interactions.

Peritoneal exudate cells from nu/nu mice stimulated with proteose peptone broth, but in general not from unstimulated mice, permitted cultures of spleen cells from congenitally athymic (nu/nu) mice to respond to the thymus-dependent antigen fowl gamma globulin (FgammaG). Supernatants of cultures of peritoneal cells were also effective, the activity being sensitive to trypsin. Since nu/nu mice were effective sources of the peritoneal cells it would not seem obligatory for the thymus-derived (T) cell to be involved in the triggering of the bone marrow-derived (B) cell by a thymus-dependent antigen FgammaG. It is proposed that the B cell is triggered at the macrophage surface where it encounters two signals (a) the antigen and (b) a protein secreted by the activated macrophage. In vivo the T cell may have a role in B-cell triggering, either in activating the macrophage or in aiding in presentation of antigen on the macrophage surface. Thymus-independent antigens are proposed to induce an IgM response because they are able to provide "signal two" either by direct interaction with the B cell or via irritation or activation of the macrophage. The stimulatory effect of T cells activated by an allogeneic interaction was used as a model of one influence of the T cell on the development of an antibody response. The presence in cultures of nu/nu spleen of an allogeneic interaction had no effect on the inability of these cells to respond to FgammaG. However when a source of the postulated second signal such as the supernatant of a macrophage culture was present, an allogeneic interaction had a powerful amplifying effect on the anti-FgammaG response. In contrast the response of nu/nu spleen cultures to heterologous erythrocytes was greatly enhanced by the presence of an allogeneic interaction. It is suggested that since there was a definite basal response to the heterologous erythrocytes added alone, the enhancement represented not an activation of more B cells but rather an amplification of this basal response. Thus the anti-FgammaG response in cultures of nu/nu spleen differentiates between factors such as those released by activated macrophages that are involved in B-cell triggering and factors released by activated T cells that amplify the numbers of antibody-forming cells resulting from a B cell already triggered.