Induction of IgG in young nude mice by lipid A or thymus grafts.

Abstract

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to LPS or lipid A; the ability to respond to lipid A with IgG production is lost between 14 and 20 days of age (unpublished results).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.

Subclass-restricted IgG polyclonal antibody production in mice injected with lipid A-rich lipopolysaccharides.

“…On the other hand, the levels of IgG2b and IgG3 in nu/nu mice were comparable to those of euthymic controls, and these levels increased after R595 LPS stimulation in parallel fashion in both groups. That nude mice normally had low levels of IgG1 and IgG2a, but not IgG2b and IgG3, as relzorted here as well as previously (37,38), and that nude mice with thymus grafts were reconstituted in respect to serum concentrations of IgG2a (30) suggest that the production of IgG 1 and IgG2a is more dependent on the presence of functional T cells than that of IgG2b and IgG3. However, our results indicate that T cell help can be replaced with LPS in reconstituting IgG1 and IgG2a to at least normal levels in immunologically deficient athymic nude mice.…”

“…That athymic C57BL/6 nude mice develop as much IgG as normal mice after the injection of R595 LPS suggests that the production of IgG polyclonal antibodies is not dependent on the presence of T cells. Such T-independent IgG production was indicated in prior studies in vitro and in newborn mice tested in vivo (10,30). However, because it is known that a few 0-bearing cells may be present in nude mice (31,32) and because LPS itself may induce precursor cells to differentiate into mature T cells (33,34), one cannot completely exclude the possible involvement of T lymphocytes in the effect that R595 LPS has on IgG production.…”

Change in the Humoral Response of Athymic Nude Mice with Ageing

“…The values for Ig levels of 1-2-month-old nude mice presented in Table I are similar to those already reported [2,4,15,17,23]. The IgM concentration is more or less increased compared with nu/-i-mice, whereas that of IgG and IgA is severely depressed.…”

“…The IgM concentration is more or less increased compared with nu/-i-mice, whereas that of IgG and IgA is severely depressed. Among the IgG subclasses, the IgGl is the lowest, the IgG2b is intermediate, whereas the IgG2a concentration increases markedly already between 1 and 3 months of age, as previously described [15]. This evolution continues for from 3 to 8 or more months and concerns all Ig classes; compared with the Ig concentration of aged nu/ -f-mice, the Ig level of aged nu/nu is about twice as high for IgM and IgG and about 0.5-fold higher for IgA.…”

The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help.

“…The A (tolerant C57BL/6) were injected with (C57BL/6 x A)F~ spleen cells intraperitoneally (i.p.). Chimerism was monitored by irnmunoglobulin allotype testing according to published methods (18).…”