Differential response of malignant human B-cells to anti-IgM immunoglobulin
(anti-mu) and B-cell growth factor: unique direct cytotoxicity of anti-mu
on prolymphocytic leukemia cells
CS Chan, F Soehnlen and GP Schechter
Hematology Section, Veterans Affairs Medical Center, Washington, DC 20422.
We examined in vitro tritiated thymidine uptake by B cells from seven
prolymphocytic leukemia (PLL), seven chronic lymphocytic leukemia (CLL),
and four plasma cell leukemia (PCL) patients in response to culture with
anti-human IgM antibody (anti-mu) and B-cell growth factor (BCGF). In
contrast to the stimulatory effect observed in normal B-cell cultures, the
divalent F(ab')2 anti-mu antibody uniquely inhibited the autonomous
proliferation and induced marked cytotoxicity in six of seven PLL cell
cultures independent of complement or Fc-receptor- mediated mechanisms.
There was neither stimulation or inhibition of the slgM+ CLL or the slgM-
PCL cells. The inhibitory effect on the PLL cells was observed at an
anti-mu concentration below the stimulatory threshold for normal B cells.
Significant impairment of trypan blue exclusion was delayed until 48 hours,
with morphological cellular changes suggestive of a programmed cell death
mechanism or apoptosis. The cytotoxicity was independent of the
slgM-staining intensity or the autonomous and BCGF-augmented DNA synthetic
activity of the PLL cells and was similar in patients with de novo PLL or
with prolymphocytic transformation of CLL. Cells from a PLL patient were
separated by elutriation into two fractions, a BCGF-unresponsive large
"transformed" cell fraction with marked autonomous DNA synthesis and a
smaller lymphoid cell subset with low 3H-thymidine uptake that could be
augmented by BCGF. Both fractions were equally susceptible to the cytotoxic
effect of anti-mu. These data suggest that certain slgM- bearing malignant
B cells are susceptible to anti-mu-triggered cytotoxicity. They may
represent the malignant counterpart of a "tolerogenic" normal B-cell
subset, and the unique direct cytotoxicity of anti-mu may provide a
therapeutic strategy specifically for PLL.
Volume 76,
Issue 8,
pp. 1601-1606,
10/15/1990
Copyright © 1990 by The American Society of Hematology
