Further studies of antigenic competition. 3. A model to account for the phenomenon based on a deficiency of cell-to-cell interaction in immune lymphoid cell populations.

A striking correlation between the capacity of an antigen to nonspecifically suppress humoral immune responses of subsequently administered antigens which are non-cross-reacting, i.e. to manifest antigenic competition and produce enlargement of spleen size through cell proliferation, was found. Increase in spleen size was always accompanied by a drop in the normal proportion of thymus-derived cells to non-thymus-derived cells. Various means of altering the immune response to the initial antigen, and hence, the capacity of that antigen to suppress in a model of antigenic competition were performed and correlated with changes in spleen size and in the proportion of theta-positive cells in the spleen. In all instances, when the experimental condition reduced or abolished antigenic competition, the increase in spleen size and reduction in the proportion of theta-positive cells in the spleen was reduced or abolished. Furthermore, under conditions in which the suppressive capacity of the initial antigen was unaltered, the increase in spleen size and reduction in theta-proportion occurred normally. Finally, the better the suppression in a model of antigenic competition, the greater the increase in spleen size and reduction in the proportion of theta-positive cells. On the basis of these observations, it appears that there is a relationship between spleen enlargement through clonally restricted cell proliferation and the expression of antigenic competition; one cannot have the latter without the former. It is postulated that the immunological lesion associated with antigenic competition resides at the level of interference with cell interaction between thymus-derived antigen-reactive cells and marrow-derived antibody-forming cells. This occurs as a result of a relative "diluting out" of cells of both populations carrying antigenic specificity differing from the one(s) which induced the dilution effect in the first place. The net effect of this is to decrease the chance of a "hit" or interaction between a marrow-derived and thymus-derived cell of the same specificities. This mechanism, which is compatible with theories of clonal selection, and which in fact is dependent upon them, supports the view that the term "antigenic competition" is a misnomer; there is no competition by the antigens for anything. The term "antigen-induced suppression" is suggested as a more suitable alternative.