Variation in DNA and RNA synthetic responses during activation of lymphocytes from inbred strains of mice

Previous studies suggested that interstrain variations in the mitogenic response of murine lymphocytes to concanavalin A (Con A), phytohemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) are genetically controlled. DNA and RNA synthesis in splenic lymphocytes from 6 inbred strains of mice were examined in response to PHA, Con A, and LPS along with other measures of lymphocyte activation. Marked variations in nucleic acid synthesis in mitogen-stimulated lymphocytes from these strains were noted when assessed by the incorporation of radiolabeled precursors into DNA or RNA. Cells from PL/J incorporated two to four times more radiolabel into DNA and RNA in response to PHA and Con A than cells from the other strains whereas cells from CBA/J, AKR/J and C57BL/6J exhibited the highest response to LPS. Variation in optimum mitogen concentration, time of peak response in culture, proportion of B and T lymphocytes, extent of the S-phase of the cell cycle, or differences in mitogen receptor affinity and number could not account for these experimental observations. There was, however, no correlation between the increases in nucleic acid synthesis and the actual number of activated lymphocytes when mitotic indices, lymphoblast numbers or number of S-phase cells were measured. Little strain variation in the number of lymphocytes activated in response to each mitogen was observed with the exception of the low response of C3H/HeJ to LPS. These studies suggest that some of the genetic variation in the incorporation of labeled precursors into nucleic acid does not reflect the number of lymphocytes activated. Measurement of DNA and RNA synthetic responses alone may not be an accurate assessment of the activation process.