Regulatory effects of IL-4 on human B-cell response to IL-2.
Interleukin-4 (IL-4) counteracts a number of the direct effects of interleukin-2 (IL-2) on B-cells. We here summarize and extend our results, obtained in two different experimental systems, on the antagonism between these two major interleukins. IL-4 inhibits the effect of IL-2 on the proliferation as well as the differentiation of B-type chronic lymphocytic leukemia (B-CLL) cells. When B-CLL cells are activated by anti-mu Ab in the presence of IL-4, this latter enhances the expression of the p55 as well as the p70/75 chain of the IL-2 receptor. In contrast IL-4 profoundly suppresses the number of high affinity binding sites for IL-2 on in vitro activated B-CLL cells. Such a discrepancy between the suppression of IL-2 binding sites and the enhancement of each component of the heterodimeric IL-2 receptor, is as far as we know, yet undescribed. The interaction of IL-4 with its own receptors might influence the state of p55-p70/75 complex association or act on a third subunit of the IL-2 receptor. When used alone, IL-4 enhances the expression of other activation molecules by B-CLL cells: CD23, DR antigen. Similarly IL-4 can concomitantly enhance the specific response of normal B-cells while suppressing the action of IL-2. When normal human B-cells are specifically stimulated by an insolubilized antigen, IL-4 alone induces an expansion of the number of specific antigen-binding cells. In contrast IL-4 profoundly suppresses the generation of antigen-induced IL-2-dependent specific IgM antibody forming cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Galanaud
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P
INSERM Unité 131.32, Clamart, France.
Karray
S
S
Llorente
L
L
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology / Q000502:physiology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D007075:Immunoglobulin M; D007376:Interleukin-2; D009363:Neoplasm Proteins; D015375:Receptors, Interleukin-2; D015847:Interleukin-4