GENETIC CONTROL OF THYMUS-DERIVED CELL FUNCTION : I. IN VITRO DNA SYNTHETIC RESPONSE OF NORMAL MOUSE SPLEEN CELLS STIMULATED BY THE MITOGENS CONCANAVALIN A AND PHYTOHEMAGGLUTININ

Concanavalin A- or phytohemagglutinin-stimulated DNA synthetic responses of 1 million normal mouse spleen cells in vitro were significantly different among various inbred strains. BALB/cJ (H-2(d)) responded better than C57BL/6J (H-2(b)) spleen cells, and the responses of C3H/HeJ or AKR/J (both H-2(k)) cells were intermediate. These responses, measured as the increment in thymidine-(3)H incorporation of mitogen-stimulated compared with unstimulated cultures, varied according to the number of cells cultured or the mitogen concentration. BALB/c spleens had the highest proportion of θ-positive cells, but no direct relationship between the proportion of θ-positive cells and the DNA synthetic response was observed. (BALB/cJ x C57BL/6)F(1) spleen cells responsed as well as BALB/c cells. Responses of spleen cells from (F(1) x C57BL/6) backcross littermates varied over a range equal to, or greater than, that of BALB/c and C57BL/6 cells. There was no correlation between H-2 specificity (H-2(bd) or H-2(bb)) or sex and the mitogen-stimulated DNA synthetic response of backcross animals. Con A- and PHA-stimulated responses of individual backcross animals were positively correlated with the level of thymidine-(8)H incorporation by unstimulated spleen cells. These results are consistent with autosomal dominant, non-H-2-linked, polygenic control of the mitogen-stimulated in vitro DNA synthetic response of mouse spleen cells.