In Vitro Regulation of the Anamnestic Antibody Response Upon Addition of Heterologous Antigens to Primed Lymphoid Cells

Alum-precipitated keyhole limpet hemocyanin (KLH) and polymerized human serum albumin (HSA) were injected into the hind foot pads of rabbits. Many months later the popliteal lymph nodes were removed and cell cultures prepared and incubated in media containing different concentrations of KLH or native HSA. These primed cells responded to some concentrations of KLH with the synthesis not only of homologous antibody but of heterologous IgG antibody to HSA. They also responded to some concentrations of HSA with the production of heterologous antibody to KLH as well as homologous antibody. In some experiments the addition of KLH induced the cells to synthesize as much antibody to HSA as did the addition of HSA itself. The nonspecific stimulation of the anamnestic antibody response to HSA required the cultures to contain KLH, HSA, KLH-reactive memory cells and, presumably memory cells reactive with HSA.

The suspension of KLH-and HSA-primed cells responded to other concentrations of KLH or egg albumin (EA) with inhibition of the antibody response to HSA. This non-specific inhibition did not require lymph node cells which had been primed by the previous injection of KLH or EA.

KLH and HSA did not cross-react with respect to immunogenicity in vitro or in vivo or reactivity with antibody in vitro.

According to a model which was proposed, the KLH induced KLH-reactive T lymphocytes to produce soluble factor(s) which regulated the response of HSA-reactive B lymphocytes to HSA-specific determinants which persisted from the original injection.