IL-13 has only a subset of IL-4-like activities on B chronic lymphocytic leukaemia cells.
The recently described interleukin-13 (IL-13) has been shown to share many of the effects of IL-4 on normal B cells, including growth-promoting activity and induction of CD23. In this study, we compared the effects of IL-13 and IL-4 on B chronic lymphocytic leukaemias (B-CLL) cells. After anti-CD40 activation, both IL-13 and IL-4 promoted the DNA synthesis of B-CLL cells and increased the recovery of viable cells. The time kinetics of the proliferative response of B-CLL cells to IL-13 or IL-4 were superimposable and showed the long-lasting effect of both cytokines. As on normal B cells, both IL-4 and IL-13 synergized with IL-10 to enhance B-CLL DNA synthesis. Moreover, IL-13, like IL-4, was able to increase CD23 expression on anti-CD40-activated leukaemic B cells. The CD23 up-regulation and the DNA synthesis induced by IL-13 on anti-CD40-activated B-CLL cells, were significantly reduced when B-CLL cells were cultured with anti-IL-4 receptor monoclonal antibody, suggesting a common pathway for IL-13 and IL-4 signalling. However, after cross-linking of surface IgM, IL-4 strongly inhibited the IL-2-induced DNA synthesis of B-CLL cells, whereas IL-13 did not inhibit IL-2-driven proliferation of anti-IgM-activated B-CLL cells. Furthermore, while IL-4 strongly up-regulated the expression of CD23 on anti-IgM-activated leukaemic B cells, IL-13 only marginally increased it. Finally, IL-13, in contrast to IL-4, did not prevent the entry of B-CLL cells into apoptosis. Thus IL-13 and IL-4 display comparable effects on anti-CD40-activated B-CLL cells, which are blocked by anti-IL-4 receptor (IL-4R) monoclonal antibodies. However, IL-13-dependent effects are absent or inefficient in non-activated or anti-IgM-activated B-CLL cells. This suggests that such cells may lack functional IL-13 receptors, though IL-13R and IL-4R on B-CLL cells share a common component.
Fluckiger
A C
AC
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Brière
F
F
Zurawski
G
G
Bridon
J M
JM
Banchereau
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007075:Immunoglobulin M; D018793:Interleukin-13; D015847:Interleukin-4; D004247:DNA