B cell growth factor-induced proliferation of hairy cell lymphocytes and
inhibition by type I interferon in vitro
KA Paganelli, SS Evans, T Han and H Ozer
Malignant B cells from hairy cell leukemia (HCL) patients are unable to
proliferate when stimulated with standard B cell mitogens. Using
chromatographically purified B cell growth factor (BCGF), HCL can be
stimulated to proliferate as assessed by incorporation of tritiated
thymidine [3HTdR] into DNA. Proliferation was found to be time dependent,
with no detectable 3H-TdR incorporation in up to three days of culture, and
significant stimulation evident at days 6 and 10. The presence of 10% BCGF
in culture was an absolute requirement for HCL proliferation; however, this
BCGF-induced DNA synthesis could be further augmented by the addition of
anti-immunoglobulin heavy chain antibodies. BCGF-induced proliferation was
abrogated in six of six patients by addition of 1,000 U/mL of recombinant
alpha 2-interferon (IFN) at day 0, although 1,000 U/mL of recombinant
gamma-IFN had no inhibitory effect in five of six patients studied.
Specific cellular receptors for type I IFN were demonstrated in HCL by
inhibition of binding of 125I-alpha 2-IFN by a 40-fold excess of unlabeled
alpha 2 or beta IFN with no inhibition by unlabeled gamma-IFN. These data
demonstrate that malignant HCL lymphoblasts express specific type I IFN
receptors and that type I, but not type II IFN, can inhibit growth
factor-induced DNA synthesis by hairy cells in vitro. They further suggest
a direct antiproliferative mechanism of action for IFN in HCL and predict
equivalent clinical activity by either alpha or beta, but not gamma IFN in
this malignancy.
Volume 67,
Issue 4,
pp. 937-942,
04/01/1986
Copyright © 1986 by The American Society of Hematology
