Lipopolysaccharide (LPS) 1 from gram-negative bacteria, or the lipid A component isolated from LPS, have a potent stimulatory effect on B lymphocytes. In vitro, they induce both cell proliferation and IgM secretion (reviewed in references 1-3). In vivo, we have demonstrated a pronounced effect of lipid A administered to mice during the first few days of life: serum IgG rose rapidly to levels 10-to 50-fold higher than in untreated controls of the same age (4). By contrast, adult animals did not show a clear response to LPS or lipid A; the ability to respond to lipid A with IgG production is lost between 14 and 20 days of age (unpublished results). The dramatic response of new-born mice to lipid A is of interest in terms of the ontogenetic development of the Ig-producing limb of the immune system. We therefore studied the early Ig production in congenitally thymusless Cnude") mice and their response to lipid A and thymus grafts. The experiments to be presented were also prompted by reports showing that the limiting factor governing the capacity of young mice to give a humoral immune response could be the presence or maturity of thymus-dependent ~'helper" cells (5,6).A number of studies in vitro are concerned with the question whether or not T cells are participants in the stimulation of B cells by LPS or lipid A (7-9). The interpretation of the results is complicated by the finding that the nude mouse does possess some 0-positive cells (10), and that, in fact, LPS itself can induce precursor cells to express T-cell-specific antigens (11).In the design of the present experiments [as with those reported previously (4)] we had to take cognizance of the fact, that young animals bear high serum levels of maternal IgG. To measure selectively the autochthonous production of IgG by the young, we had to use allotypically heterozygous offspring, and assay only the Ig bearing the paternal allotype.The experiments show that lipid A can induce accelerated IgG production in young nudes, albeit not to the same degree as in normal young mice. IgG production was also dramatically stimulated by nearly congeneic thymus grafts; and the effects of lipid A and thymus grafts were additive and possibly cooperative.
Materials and MethodsMice. The following mice were bred in our laboratory: BALB/c-AnNIcr; BALB/c-nu, a backcross-line developed in Konstanz by B. M. Kindred, which carries the nude (athymic) factor on the * Supported by the ¢'Sonderforschungsboreich 138" of the Deutsche ForschungsgemeinschaR.