Genetic Control of Responses to Bacterial Lipopolysaccharides in Mice

In vivo immune responses and in vitro mitogenic responses to bacterial lipopolysaccharides (LPS) have been compared in strains of C3H mice. C3H/HeJ spleen cultures did not support mitogenic responses to LPS and in vivo these mice produce low IgM responses to LPS. On the basis of these two responses, C3H/HeJ mice have been termed low LPS responders. All other strains of C3H mice tested (C3HeB/FeJ, C3H/DiSn, C3H/Str, CWB, CSW, and C3H/Sf and its H-2 congenics) are high LPS responders supporting large in vitro mitogenic and in vivo immune responses to LPS. The immune response difference between low and high LPS responders is a quantitative one. IgM responses are observed in C3H/HeJ mice in the range of 1.0-10 microg LPS. At lower and higher LPS concentrations, immune responses are not observed. In contrast, high LPS responders elicit LPS immune responses over a much wider dose range (0.1-200 microg). The ability to respond well to LPS is dominant as shown by the response of F(1) hybrid mice of low responder and high responder strains. The linkage relationships of mitogenic and immune responsiveness to LPS have been investigated in backcross (C3H/HeJ x CWB)F(1) x CWB mice. All mice that gave in vivo immune responses to LPS also supported mitogenic responses to LPS. The defect in C3H/HeJ mice that limits mitogenic and immune responsiveness to be due to a single autosomal gene which is not linked to the H-2 histocompatibility or heavy-chain allotype loci.