IL-4 inhibits the expression of high affinity IL-2 receptors on monoclonal human B cells.
In the presence of anti-mu antibodies (anti-microAb), monoclonal B lymphocytes from patients suffering from B type chronic lymphocytic leukemia (B-CLL) can respond to IL-2. In contrast to the effect it exerts on normal B cells, IL-4 does not promote DNA synthesis by B-CLL lymphocytes. Rather this interleukin inhibits the response to IL-2 in all patients' cells that responded to this interleukin. We thus examined whether IL-4 would modulate the number and/or the affinity of IL-2 receptors. A 3-day activation of cells by anti-microAb induced a few hundred high affinity IL-2 receptors (HA-IL-2R) on B-CLL cell surface, as determined by Scatchard analysis. Treatment of cells with IL-4 caused a marked decrease in the number of HA-IL-2R without interfering with the binding ability of IL-2. In contrast with this profound suppressive effect, IL-4 did not down-regulate the expression of each chain, alpha and beta (p55 and p75, respectively), of the HA-IL-2R heterodimer. In fact, the expression of alpha and beta induced by anti-microAb was enhanced by IL-4. Altogether, IL-4 exerts a critical influence on the function and the configuration of HA-IL-2R without inhibiting the expression of two subunits, alpha and beta.
Karray
S
S
Institut National de la Santé et de la Recherche Médicale U 131, Clamart, France.
Dautry-Varsat
A
A
Tsudo
M
M
Merle-Beral
H
H
Debre
P
P
Galanaud
P
P
D001402:B-Lymphocytes / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000032:analysis*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015847:Interleukin-4