Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides

Lipopolysaccharides (LPS) from E. coli bacteria were found to be mitogenic for bone marrowderived (B) lymphocytes, but had no effect on thymusderived (T) lymphocytes. When added to normal spleen cells in culture, LPS selectively stimulated the secretion of 19 S proteins, whereas there was no demonstrable increase of 7 S protein synthesis. Spleen cell cultures treated with various doses of LPS exhibited atypical dose response curve with regard to induction of DNA synthesis, 10 μg/ml being optimal, higher and lower concentrations giving lower responses. When direct antibody producing cells to horse and sheep red cells were studied in normal spleen cell cultures exposed to different concentrations of LPS in vitro, it was found that their number increased in parallel with stimulation of DNA synthesis. In contrast, the number of antibody producing cells to LPS itself did not parallel activation of DNA synthesis. Spleen cells from LPS tolerant animals responded with increased numbers of antibody producing cells to heterologous red cells after treatment with LPS in vitro to the same extent as normal spleen cells. Thus, a B cell mitogen, such as LPS, could activate division in B cells, resulting in an increased number of cells producing antibodies to non-cross-reacting antigens, mimicing the effect of specific antigen.