Effect of Lipopolysaccharide on Immunogenicity and Tolerogenicity of HGG in C57BL/6J Nude Mice: Evidence for a Possible B Cell Deficiency

Studies were performed to define the in vivo and in vitro responsiveness of nude mice to bacterial lipopolysaccharide (LPS). The in vitro responsiveness to LPS of spleen cells from congenitally athymic nude C57BL/6J mice was equivalent to littermate cells when monitored by stimulation of mitogenesis or polyclonal activation. Additionally, although nude spleen cells were incapable of responding to in vitro challenge with the T-dependent antigen, sheep red blood cells (SRBC), the addition of LPS to these cultures promoted specific antibody synthesis indicating classical responsiveness of nude B cells to LPS in vitro . The effects of LPS upon responsiveness to human γ-globulin (HGG) in vivo were also investigated. The injection of deaggregated HGG (tolerogen) into nude mice was demonstrated to induce immune tolerance in the splenic B cells of these mice. This unresponsive state was stable upon transfer into primed, irradiated recipients and persisted in the nude mice for up to 4 months. The induction of this tolerant state established in the absence of detectable T cell activity could be inhibited by the injection of LPS 3 hr after the tolerogen. Although LPS was capable of inhibiting the induction of tolerance in nude mice in vivo , it was incapable of promoting the generation of specific antibody-secreting, plaque-forming cells (PFC) to either HGG or SRBC when injected with these T-dependent antigens. This failure of LPS to replace the requirement for T cells in the production of the PFC response to these antigens did not extend to AT × BM littermate mice. Additionally, LPS itself was recognized as a T-independent antigen by these nude mice. Although the induction of tolerance in the B cells of nude mice demonstrated that T cells are not required for the induction or maintenance of B cell tolerance, the inability of nude B lymphocytes given LPS to respond to T-dependent antigens indicated that the signal received by B cells from the LPS molecule which replaces the requirement for helper T cells may be distinct from other LPS signals. Furthermore, the data from several experimental approaches suggested that nude mice may be deficient in a subpopulation of B cells which is responsive to both antigen and nonspecific B cell activators in normal mice.