Interleukin-12 up-regulates the induction of an antigen-specific antibody response in cultures of human lymphocytes

The influence of interleukin-12 (IL-12) on the induction of a specific antibody response to the T-dependent antigen sheep erythrocytes (SRBC) in cultures of human blood lymphocytes was investigated. The response, evaluated as number of antigen-induced antibody-producing cells, was greatly increased in the presence of IL-12. When a two-stage limiting dilution culture system was used, the plot of the number of seeded cells versus the logarithm of the fraction of negative cultures deviated from linearity in antigen- and IL-12-stimulated cultures. However, linearity was reached when IL-2 was added in the second stage. Under these latter conditions, since single-hit criteria were fulfilled, it was possible to estimate the frequency of SRBC-specific B cell precursors able to respond to the antigen and to show that such frequency was increased upon addition of IL-12. Thus, the enhancing effect of IL-12 may be based on an increased frequency of responding precursor cells. The results here presented demonstrate, to our knowledge for the first time, a definite role of IL-12 in the induction of a specific antibody response in human cells. Further, they stress the importance for such studies of appropriate in vitro systems. Finally, they show that the induction of primary immune responses in cultures of human peripheral blood lymphocytes mostly depends on the proper cytokine balance at different time points.