DUAL EFFECTS OF INTERLEUKIN-4 ON ANTIGEN-ACTIVATED HUMAN-B CELLS - INDUCTION OF PROLIFERATION AND INHIBITION OF INTERLEUKIN 2-DEPENDENT DIFFERENTIATION

We analyzed the effects of interleukin 2 (IL 2) and IL 4 isolated and in association on the specific response of human B cells triggered by trinitrophenylated polyacrylamide beads (TNP‐PAA). IL 2 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]. IL 4 induced an isolated RFC response without PFC response. We verified that the IL 4 (as well as I2)‐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. IL 2 appeared to drive more B cells into the intermediate density fraction. IL 2‐induced PFC belonged to the RFC population and were intermediate‐size B cells. IL 2 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, IL 4 inhibited the IL 2‐dependent PFC without affecting the number of RFC nor the proportion of proliferating RFC induced by this IL. These results directly demonstrate that human IL 4 triggers the expansion of antigen‐activated B cells and selectively inhibits the IL 2‐induced differentiation. Copyright © 1990 Wiley‐VCH Verlag GmbH & Co. KGaA