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 12)-induced RFC were hapten specific and mediated through membrane IgM. Density fractionation experiments showed that IL 4-induced RFC were equally distributed between high-density 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.
INSERM U 131, Clamart, France.
L
L
Llorente
F
F
Mitjavila
M C
MC
Crevon
P
P
Galanaud
D000921:Antibody-Producing Cells / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002458:Cell Fractionation; D006241:Haptens / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*
D006241:Haptens; D007376:Interleukin-2; D015847:Interleukin-4