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The proliferative response of B cell chronic lymphocytic leukemia to
interleukin 2: functional characterization of the interleukin 2 membrane
receptors
I Touw, L Dorssers and B Lowenberg
To determine the growth properties of B cell chronic lymphocytic leukemia
(B CLL) and to identify possible abnormalities thereof, we examined the in
vitro action of interleukin 2 (IL2) in four patients. Using radiolabeled
IL2 and monoclonal antibodies reactive with IL2 membrane receptors we show
that CLL cells, after their activation in vitro, express IL2 receptors of a
high- as well as a low-affinity type, exactly as has been reported for
normal T and B blasts. In three of the four reported cases, CLL
proliferation (measured with 3H-thymidine incorporation) depended on the
addition of phytohemagglutinin (PHA) to activate the cells and IL2 (optimal
concentration, 10 to 100 U IL2/mL). In contrast, the cells of the fourth
case of CLL (CLL-4) proliferated in an autonomous fashion, ie, without a
need for PHA and IL2 in culture. Specific blocking of the IL2-binding sites
with anti-IL2 receptor monoclonal antibodies almost completely inhibited
the proliferation of these cells, which indicated that functional IL2
receptors were required for the autonomous proliferation. The demonstration
of low concentrations of IL2 activity in the culture medium conditioned by
the cells suggests that endogenous IL2 had been responsible for the
spontaneous 3H-thymidine uptake by the CLL cells of patient 4. However, we
were unable to extract IL2 mRNA from the cells (neither fresh nor after
various in vitro incubations) in quantities detectable by Northern blot
analysis that would prove that the CLL cells of patient 4 were actively
synthesizing IL2 during culture. Thus, individual cases of B CLL are
subject to variable growth regulation involving functional IL2 receptors on
the cell surface: after activation with PHA the cells respond to exogenous
IL2 in a fashion similar to normal B lymphocytes, or the cells are
stimulated by endogenous IL2 (or an IL2-like activity) and do not require
activation with PHA.
Volume 69,
Issue 6,
pp. 1667-1673,
06/01/1987
Copyright © 1987 by The American Society of Hematology
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