Immunogenicity, Tolerogenicity, and Mitogenicity of Lipopolysaccharides

Abstract

Lipopolysaccharide (LPS) is an immunogen that often induces synthesis of IgM only, and these antibodies exhibit regular cyclical fluctuations due to an antibodymediated feed-back regulation. LPS can induce high-dose immunologic tolerance; however, tolerant animals have an increased number of antigen-binding cells, even though the number of antibody-producing cells is depressed. Tolerance to LPS is rapidly broken by incubation of lymphocytes in tissue culture for 24 hr or by adoptive transfer of tolerant cells to irradiated hosts, suggesting the existence of cells tolerant to this antigen. LPS is also a mitogen capable of activating DNA synthesis in bone-marrow (B) cells but not in thymus (T) cells. LPS-activated B cells secrete IgM antibodies against a variety of antigens. It is most likely that LPS-activated B lymphocytes differentiate into cells that produce antibody at a high rate and that express their genetically determined antibody specificity. When LPS is coated onto T-cell-dependent, heterologous red cells, the latter become T-cell-independent, presumably because of the mitogenic properties of LPS. LPS can substitute for both T cells and macrophages in the induction of a primary immune response in vitro, suggesting that LPS acts directly on B cells and that at least one function of the helper is immunologically nonspecific.