We analyzed the effects of interleukin 2 (IL2) and IL4 isolated and in association on the specific response of human B cells triggered by trinitrophenylated polyacrylamide beads (TNP-PAA). IL2 induced an increase (more than 10 times) in the number of hapten-binding cells [detected by a rosette-forming cell (RFC) assay] as well as the generation of antibody-producing cells [detected by a plaque-forming cell (PFC) assay]. IL4 induced an isolated RFC response without PFC response.We verified that the IL4 (as well as 12)-induced RFC were hapten specific and mediated through membrane IgM. Density fractionation experiments showed that IL 4-induced RFC were equally distributed between highdensity and intermediate-density B cells. IL2 appeared to drive more B cells into the intermediate density fraction. ILZinduced PFC belonged to the RFC population and were intermediate-size B cells. IL2 drove more RFC into an activated stage and it induced the differentiation of a number of them into antibody-producing cells. The evaluation of the proportion of RFC able to incorporate thymidine showed that both IL induced a substantial proliferation of antigen-activated B cells. However, IL4 inhibited the IL 2-dependent PFC without affecting the number of RFC nor the proportion of proliferating RFC induced by this 1L.These results directly demonstrate that human IL 4 triggers the expansion of antigen-activated B cells and selectively inhibits the IL 2-induced differentiation.
* This work was supported by INSERM and by UniversitC de 2 Materials and methods
2.1 Reagents
Human rIL 2 was a gift from Biogen SA (Geneva, Switzerland). The preparation used had a specific activity of Paris-Sud.