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Y Levy, S Labaume, MC Gendron and JC Brouet
Laboratory of Immunopathology, Hopital Saint-Louis, Paris, France.
We previously showed that clonal blood B cells from patients with
macroglobulinemia spontaneously differentiate in vitro to plasma cells.
This process is dependent on an interleukin (IL)-6 autocrine pathway. We
investigate here whether all-trans-retinoic acid (RA) interferes with
B-cell differentiation either in patients with IgM gammapathy of
undetermined significance (MGUS) or Waldenstrom's macroglobulinemia (WM).
RA at a concentration of 10(-5) to 10(-8) mol/L inhibited by 50% to 80% the
in vitro differentiation of purified B cells from four of five patients
with MGUS and from one of five patients with WM as assessed by the IgM
content of day 7 culture supernatants. We next determined whether this
effect could be related to an inhibition of IL- 6 secretion by cultured B
cells and/or a downregulation of the IL-6 receptor (IL-6R), which was
constitutively expressed on patients' blood B cells. A 50% to 100% (mean,
80%) inhibition of IL-6 production was found in seven of 10 patients (five
with MGUS and two with WM). The IL- 6R was no more detectable on cells from
patients with MGUS after 2 days of treatment with RA and slightly
downregulated in patients with WM. It was of interest that B cells
susceptible to the action of RA belonged mostly to patients with IgM MGUS,
which reinforces our previous data showing distinct requirements for
IL-6-dependent differentiation of blood B cells from patients with VM or
IgM MGUS.
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| Copyright © 1994 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||