Monoclonal antibodies coupled to LPS specifically induce synthesis of immunoglobulins with complementary variable region determinants.

The aim of this work was to investigate whether LPS coupled to monoclonal immunoglobulins would, at certain critical doses, specifically trigger B cells carrying immunoglobulins with V region complementary to that of the immunogen. Thus sera of BALB/c mice injected with 5 micrograms of LPS-M-460 contained immunoglobulins that specifically reacted with the M-460 protein. Similarly, injection of LPS coupled to a monoclonal anti-M-460 immunoglobulin F6(51) resulted in the selective production of antibodies specific for F6(51). In addition, radioimmunoassay studies clearly showed that the induced immunoglobulins reacted with F6(51) through idiotypic interactions. This immune response is independent from T cells because nu/nu responded as well as their heterologous littermates. Kinetic studies showed that the titer of F6(51) complementary antibodies in mice injected with F6(51)-LPS remained elevated for more than 1 mo, and that the majority of these immunoglobulins belong to the IgM class. Surprisingly, F6(51)-LPS induced F6(51)-specific antibodies only in mice with the Igh-a allotypic haplotype, indicating that although thymus-independent, the response is under regulation. Finally, addition of small amounts of F6(51)-LPS to cultures of B cells from BALB/c mice resulted in the secretion of antibodies capable of reacting with F6(51). These low concentrations failed to activate nonspecific cells. Consequently our data offer the possibility of selectively inducing in vivo or in vitro idiotype-positive immune responses in the complete absence of the antigen recognized by the induced immunoglobulins.