Regulation of antibody synthesis against Escherichia coli endotoxin. II. Specificity, dose requirements and duration of paralysis induced in adult mice.

Adult mice were paralysed with high doses of detoxified lipopolysaccharide of 055:B5. The immune status of the animals was tested by enumeration of antibody producing spleen cells using the agar plaque technique and by measurements of serum antibody titres. Paralysis was specific as judged by the ability of paralysed animals to respond normally to sheep red blood cells. The range between paralysing and immunizing doses of endotoxin was narrow, injection of 10 mg endotoxin inducing complete paralysis and of 1 mg causing immunity. Repeated injections of doses lower than 10 mg were shown to induce complete paralysis when the total dose was sufficiently high. Repeated injections of even lower doses caused various degrees of partial paralysis. A single injection of a low dose (10 or 10 mg) of the antigen resulted in a maximal number of antibody forming cells, whereas various higher doses caused fewer antibody producing cells to appear, presumably because of concomitant induction of partial paralysis. The maximal number of antibody forming cells developed earlier with lower doses of antigen. The delay in the peak response with higher doses was explained by a decreased efficiency of antibody feedback suppression caused by induction of partial paralysis as well as by absorption of antibodies to circulating antigen.