The mechanism of antigenic competition. I. The macrophage as a site of a reversible block of T-B lymphocyte collaboration.

A model of antigenic competition, initiated in vivo, but expressed in vitro, was developed in order to study the cellular basis of antigenic competition. This was initiated by the injection of donkey or chicken red cells 2 days before sacrifice. To permit a response to a thymus dependent hapten protein conjugate in vitro, it was necessary to prime the mice with the carrier some weeks prior to culture. Thus the response of mice primed with fowl gamma globulin (FGG) to dinitrophenylated (DNP) FGG in vitro was used as the test for antigenic competition. The function of B cells was found to be normal, since the response to a thymus independent antigen, DNP flagella of Salmonella adelaide, was found to be normal, while that to DNP FGG was suppressed. The locus of suppression in antigenic competition was found to be the macrophage, since small numbers (3000) of peritoneal cells which had been depleted of T cells by treatment with anti theta serum and complement restored the response to DNP FGG. Trypsinization of the spleen populations also overcame antigenic competition, indicating that there was no irreversible block of any cell type. Trypsinization did not augment the in vitro response to DNP FGG of noninjected mice or that to DNP FLA of normal or DRC injected mice. Thus, trypsinization overcame competition without augmenting the response of either T or B cells and thus acted to remove a surface inhibitor from the surface of macrophages. The results were interpreted in the light of current concepts of the mechanism of T B collaboration. It is proposed that antigenic competition is a byproduct of the release of complexes of IgT and antigen by T cells. These bind to macrophages, initiating the response to the first antigen, but competing out the binding of IgT complexes to a subsequently administered antigen which are needed to trigger B cells and thus blocking the cooperative response to the second antigen