Interleukin 4 inhibits the proliferation but not the differentiation of activated human B cells in response to interleukin 2.
The combined effect of IL-4 and IL-2 on proliferation of anti-IgM antibody or Staphylococcus aureus strain Cowan I (SAC)-preactivated B cells was investigated. It was observed that in most cases, rIL-2 used at optimal concentration induced higher levels of tritiated thymidine ([3H]TdR) uptake than rIL-4 used at optimal concentration. When rIL-4 and rIL-2 were added together, it was repeatedly found that B cell proliferation induced by rIL-2 was significantly reduced and was, in most cases, comparable with the proliferation induced by rIL-4 alone. Cell cycle studies demonstrated that rIL-4 significantly reduced the number of cells entering S and G2/M phases of the cell cycle upon rIL-2 stimulation. B cell blasts preincubated for 24 or 48 h with rIL-4 displayed a reduced proliferation in response to rIL-2. In contrast, preculture of resting B cells with rIL-4 did not impair their subsequent proliferation in response to rIL-2 plus insolubilized anti-IgM antibody. This suggests that rIL-4 can only exert its inhibitory effect once B cells have received an activation signal. The differentiative activity of rIL-2 measured on B cell blasts preactivated for 2 d with SAC was not altered by rIL-4, which suggests that rIL-4 did not exert its inhibitory activity on rIL-2-induced B cell proliferation by enhancing rIL-2-mediated differentiation. Delayed addition of a neutralizing anti-IL-4 antiserum demonstrated that a period of contact of at least 24 h between IL-4 and B cell blasts was necessary for the development of the antagonistic effect of IL-4 on IL-2-mediated growth of activated B cells. These data demonstrate that IL-4 antagonizes the B cell growth-promoting effect of IL-2 without affecting the differentiation of preactivated B cells in response to IL-2.
Defrance
T
T
UNICET, Laboratory for Immunological Research, Dardilly, France.
Vanbervliet
B
B
Aubry
J P
JP
Banchereau
J
J
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000166:cytology; D011994:Recombinant Proteins / Q000494:pharmacology
D007106:Immune Sera; D007376:Interleukin-2; D007378:Interleukins; D011994:Recombinant Proteins; D015847:Interleukin-4