Synthesis of immunoglobulin by normal and antigenically stimulated fetal sheep.

The rate of appearance, quantity and immunochemical character of serum immunoglobulins which appear normally during the development of fetal sheep and following the injection of antigens at different stages of gestation have been studied. After 70 days' gestation a percentage of normal fetal sheep synthesise IgM. Although the concentration of IgM in the circulation of these animals was very low, the precentage with IgM increased with fetal age. A few late term fetuses were detected which also had IgG1 in their circulation, although none were detected with IgG2 or IgA. Fetuses injected with antigens before 71 days' gestation only synthesised IgM, while fetuses injected after 79 days' gestation synthesised both IgM and IgG1. Neither IgG2 nor IgA were detected by single-radial immunodiffusion analyses during the first 14 days of primary immune responses to a variety of antigens, although trace amounts of IgG2 were detected late in responses occurring in older fetuses. The immunoglobulins synthesised by antigenically stimulated fetal sheep appeared identical to adult sheep 19S IgM, 7S IgG1 and 7S IgG2 respectively, when analysed by immunoelectrophoresis, isoelectric focusing and G200 Sephadex column chromatography.     

Tolerance breaking by lymphocyte activating factor induced by Escherichia coli O138 lipopolysaccharide from homologous macrophages.

Following an antigenic dose of 10 microgram or a tolerogenic dose of 200 microgram of Escherichia coli O138 lipopolysaccharide (LPS), BALB/c mice were examined on day 14 for percentages of theta-bearing cells. A considerable increase in T cells was noticed in lymphocytes from tolerant draining lymph nodes, and furthermore these cells did not possess receptors for LPS when tested for rosette inhibition. However, when the supernatant from 1 X 10(7) macrophages, pretreated with 150 microgram LPS, was given to tolerant mice on day 7, by day 14 tolerance was found to be broken, anti-LPS IgG was present in circulation and the draining lymph node contained T cells specifically committed to LPS. The change from suppressor to helper T cell activity is discussed in relation to enhancement of the immune response.