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-2d) responded better than C57BL/6J (H-2b) spleen cells, and the responses of C3H/HeJ or AKR/J (both H-2k) cells were intermediate. These responses, measured as the increment in thymidine-3H 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)F1 spleen cells responsed as well as BALB/c cells. Responses of spleen cells from (F1 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-2bd or H-2bb) 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-8H 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.

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