A Model for the Interaction of Cell Types in the Generation of Hemolytic Plaque-Forming Cells

Abstract

The results of limiting-dilution and dose-response experiments involving the primary immune response of dispersed mouse spleen cells in Millipore diffusion chambers are presented. Sheep erythrocytes were employed as antigen and the immune response assessed by the enumeration of hemolytic plaque-forming cells using the classical Jerne technique. Limiting-dilution analysis demonstrated that the number of “response units” involved in initiating the immune response was a linear function of the spleen cell dose. The frequency of these response units in the antigen-stimulated spleen cell population was also estimated. Logarithmic dose-response curves dealing with the magnitude of the immune response as a function of spleen cell dose were found to be biphasic. At low doses of spleen cells the magnitude of the response was a nonlinear function of the cell dose, but this relationship abruptly became linear at higher spleen cell doses. A stochastic model for the initiation of the immune response based on the interaction of two cell types is proposed and this model is compatible with the findings of both limiting-dilution analysis and dose-response experiments. This model suggests that a response unit is formed by the multiplicative interaction of precursors of antibody-forming cells with antigen-reactive cells, the former cells becoming transformed into antibody-forming cells through such an interaction. That is, an individual antigen-reactive cell is able to interact with and influence the transformation of more than one precursor cell and the number of precursor cells transformed per antigen-reactive cell is a function of the spleen cell dose.