Tetanus toxoid complexed with heterologous antibody can induce germinal centre formation and B cell memory in mice without evoking a detectable anti-toxin response

Fluid free tetanus toxoid (FTT) alone or FTT complexed in vitro at equivalence (EQ) or in antibody excess (ABEX) with anti-toxin contained in a human gammaglobulin preparation (HGG), or HGG alone, were injected into the hind leg footpads of mice. Anti-toxin titres of mouse serum were measured and compared with proliferative reactions in popliteal lymph nodes, based on combined 3H-thymidine autoradiography and planimetry, as a function of time. FTT in complex with HGG in ABEX failed to elicit a measurable anti-toxin response but caused, of all the materials tested, the most marked numerical increase of germinal centres. This finding is in accord with results of earlier studies indicating that the same heterologous antigen-antibody complexes at EQ or in ABEX can prime the animals, usually without eliciting antibody production detectable by serum titration. The model system used in the present experiments is thus well suited for a separation of the two principal arms of the dichotomous humoral immune response, i.e. by inducing germinal centre and B cell memory development but not specific antibody formation.