Strain differences in the proliferative response of murine spleen cells to mitogen.

Abstract

Responses to the T cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) of mouse spleen cells were studied. C57BL/6 (B6) mice were low, Balb/c (C), C3H, CBA, DBA/1,129 and AKR were high and DBA/2 and C57BR were intermediate responders. Responses of cells from BIO and its congenic resistant strain mice were similar to those of B6 cells. Differences in <sup>3</sup>H-thymidine uptake of cells from low and high responders were larger at high than at optimal mitogen doses. Cells from low responders were very sensitive to the inhibitory effect of high doses of mitogen. Thus, doses of Con A and PHA which caused inhibition of DNA synthesis and the shut-off of the dose-response curve of B6 cells stimulated high proliferative activity of cells from high responders. Similar variations in the optimal response and the shape of the dose response curve were observed at different culture times. Depletion of adherent cells (AC) depressed the response to suboptimal doses of mitogen of either low responder B6 or high responder C spleen cells, but determined marked enhancement of the response to high mitogen doses of B6 spleen cells. However, the response to high mitogen doses of C spleen cultures was not significantly modified by similar treatment. It is suggested that strain variations in the optimal response to PHA and Con A and in the sensitivity to inhibition of DNA .synthesis by high doses of mitogen depend on differences in the regulatory capacity of AC, or on the susceptibility of the responsive cell population to the inhibitory effect of AC.