Analysis of the cell populations capable of initiating a response to sheep and horse erythrocyte antigens has been carried out by means of equilibrium density gradient centrifugation. The results indicate that there are at least six distinguishable AS cell populations for sheep erythrocytes, but only three for horse erythrocytes in the spleen of the Lewis rat. Evidence is presented for the existence of metabolic, physiological, and immunological differences among these populations. It is suggested that at least one population of AS cells responds only to the specific antigen and at least one other population is sensitive to stimulation by a broad range of antigens. It is assumed that the difference between these two AS cells results from a process of differentiation of AS cells primed into DNA synthesis by antigen stimulation.

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